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rs104894396

Variant summary

Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_004004(GJB2):c.71G>A(p.Trp24Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 152178 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 1 hom. )

Consequence

GJB2
NM_004004 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic reviewed by expert panel P:40B:2

Conservation

PhyloP100: 7.85

Links

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 16 ACMG points.

PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. There are 234 pathogenic variants in the truncated region.
PP5
?
Variant 13:20189511-C>T is Pathogenic according to our data. Variant chr13-20189511-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 17002. Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-20189511-C-T is described in Lovd as [Likely_pathogenic]. Variant chr13-20189511-C-T is described in Lovd as [Pathogenic]. Variant chr13-20189511-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GJB2NM_004004.6 linkuse as main transcriptc.71G>A p.Trp24Ter stop_gained 2/2 ENST00000382848.5
GJB2XM_011535049.3 linkuse as main transcriptc.71G>A p.Trp24Ter stop_gained 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GJB2ENST00000382848.5 linkuse as main transcriptc.71G>A p.Trp24Ter stop_gained 2/21 NM_004004.6 P1
GJB2ENST00000382844.2 linkuse as main transcriptc.71G>A p.Trp24Ter stop_gained 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152178
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000584
AC:
146
AN:
250040
Hom.:
1
AF XY:
0.000732
AC XY:
99
AN XY:
135286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00438
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000623
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000294
AC:
430
AN:
1461884
Hom.:
4
AF XY:
0.000397
AC XY:
289
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00419
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.000613
Alfa
AF:
0.0000442
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.000576
AC:
70
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:40Benign:2
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 1A Pathogenic:18
Pathogenic, criteria provided, single submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaMay 09, 2017- -
Pathogenic, criteria provided, single submitterclinical testingSuma Genomics-- -
Pathogenic, criteria provided, single submitterclinical testingVictorian Clinical Genetics Services, Murdoch Childrens Research InstituteOct 19, 2020Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. Multiple truncating variants have previously been reported pathogenic (ClinVar). (N) 0108 - This gene is known to be associated with both recessive and dominant disease (OMIM). (N) 0204 - Variant is predicted to result in a truncated protein with more than 1/3 of the protein affected (exon 2 of 2). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (145 heterozygotes, 1 homozygote). (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Multiple truncating variants have been previously reported pathogenic (ClinVar) (P) 0801 - Strong previous evidence of pathogenicity in unrelated individuals. This variant has previously been reported in multiple independent cases (ClinVar). (P) 1002 - Moderate functional evidence supporting abnormal protein function. This variant has been shown to result in stop codon readthrough, affecting cellular localisation of the protein (PMID 18941476). (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -
Pathogenic, no assertion criteria providedresearchKasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, IndiaMay 15, 2018- -
Pathogenic, criteria provided, single submitterresearchHudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for BiotechnologyDec 08, 2016- -
Pathogenic, criteria provided, single submitterresearchHudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for BiotechnologyApr 12, 2021ACMG codes:PVS1, PM2, PP5 -
Pathogenic, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJun 28, 2016Variant summary: The GJB2 c.71G>A (p.Trp24X) variant results in a premature termination codon, predicted to cause a truncated or absent GJB2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Functional analysis showed that this results into truncated protein; the mutant protein does not undergo nonsense mediated decay (Mani_2009). Thus it causes loss of connexin and gap junction channel protein cysteine-rich domains. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.p.Trp44X, p.Gln124X, etc.). This variant was found in 70/121380 control chromosomes at a frequency of 0.0005767, which does not exceed the estimated maximal expected allele frequency of a pathogenic GJB2 variant (0.025). In literature, this variant is reported as one of the common pathogenic variants, found especially in India, with consistent clinical (cosegregation and genotypic) data supporting for pathogenicity. Multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitterclinical testingLaboratory of Medical Genetics, National & Kapodistrian University of AthensMay 20, 2018PS3, PM1, PM4, PP2, PP3 -
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 01, 2005- -
Pathogenic, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017The GJB2 c.71G>A (p.Trp24Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. Across a selection of the available literature, the p.Trp24Ter variant has been identified in at least 46 patients with a recessive form of nonsyndromic hearing loss including in 28 in a homozygous state, 12 in a compound heterozygous state, and 6 in a heterozygous state (Kelsell et al. 1997; Maheshwari et al. 2003; RamShankar et al. 2003; Alvarez et al. 2005; Salman et al. 2015). The variant has been shown to segregate with disease in an autosomal recessive pattern in affected families (Maheshwari et al. 2003). The p.Trp24Ter variant was reported in five of 285 controls in a heterozygous state, which is consistent with carrier frequency, and is reported at a frequency of 0.00399 in the South Asian population of the Exome Aggregation Consortium. RamShankar et al. (2003) found that the p.Trp24Ter variant was the most common variant among 215 Indian probands and suggested a founder effect was responsible for the estimated carrier frequency of 0.024 in the Indian population. The variant has not been reported in association with Vohwinkel syndrome, ichthyosis hystrix-like with deafness, keratitis-ichthyosis-deafness syndrome or the dominant form of nonsyndromic hearing loss, all conditions known to be caused by variants in the GJB2 gene. Based on the disease prevalence and frequency of the variant, the p.Trp24Ter variant can be ruled out of causing disease in these conditions despite the potential impact of stop-gained variants. However, based on the collective evidence, the p.Trp24Ter variant is classified as pathogenic for the recessive form of nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Pathogenic, criteria provided, single submitterclinical testingLifecell International Pvt. Ltd-A Homozygote Nonsense variant c.71G>A in Exon 2 of the GJB2 gene that results in the amino acid substitution p.Trp24* was identified. The observed variant has a minor allele frequency of 0.00058 in gnomAD exomes and 0.00003 in genomes. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variation ID: 17002]. The observed variation has been previously reported in patients affected with Deafness (Kecskeméti, Nóra et al., 2018). For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Pathogenic, criteria provided, single submitterclinical testingMyriad Genetics, Inc.Nov 12, 2019NM_004004.5(GJB2):c.71G>A(W24*) is classified as pathogenic in the context of GJB2-related DFNB1 nonsyndromic hearing loss and deafness. Sources cited for classification include the following: PMID 15070423, 19371219, 15967879, 18941476 and 22695344. Classification of NM_004004.5(GJB2):c.71G>A(W24*) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. -
Pathogenic, criteria provided, single submitterclinical testingIntegrating Genomics into Medicine, Frazer Institute, University Of QueenslandJun 02, 2023- -
Pathogenic, criteria provided, single submitterclinical testingBreda Genetics srlJun 29, 2021The variant c.71G>A (p.Trp24*) in the GJB2 gene is reported as a pathogenic for GJB2-related autosomal recessive deafness in ClinVar (Variation ID: 17002). This mutation has been described in multiple papers and is considered common in the Pakistani and Indian population (Richard et al., 2019, PMID: 30303587; Shaik et al., 2017, PMID: 29086887; Santos et al., 2005, PMID: 15617550). It creates a premature stop codon at amino acid position Trp24, which is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). The variant is reported with an estimated allelic frequency of 0.0006 in gnomAD exomes and 0.0000319 in gnomAD genomes, with one homozygous individual reported. -
Pathogenic, no assertion criteria providedresearchDivision of Human Genetics, Children's Hospital of PhiladelphiaJun 23, 2014The variant (c. 71G>A, p. W24*) has been previously associated with autosomal recessive hearing loss (Kelsell et al. 1997, PMID: 9139825; Maheshwari et al. 2003, PMID: 12833397; Minarik et al. 2003, PMID: 15113126; Roux et al. 2004, PMID: 15070423; Toth et al. 2004, PMID: 15146474; Alvarez et al. 2005, PMID: 16088916; Bouwer et al. 2007, PMID: 18294064). This variant has been described as the most common GJB2 variant in individuals of Indian descent (2.4% carrier frequency) and Roma descent (4-5% carrier frequency) (Bouwer et al. 2007, PMID: 18294064). This variant is a nonsense variant predicted to create a premature stop codon. Functional analysis suggests that this variant affects the gap junction activity (Mani et al. 2009, PMID: 18941476). Taken together this variant is considered a pathogenic variant. -
Pathogenic, criteria provided, single submitterclinical testing3billionMay 22, 2022The substitution creates a nonsense variant within 50 bp downstream of the penultimate exon or last exon. While it is expected to escape nonsense-mediated decay, the truncated region is considered critical. Functional assays showed that the variant had strong level of impact on gene/protein function (PMID: 18941476).This variant has been reported as pathogenic multiple times (ClinVar ID: VCV000017002,PMID:9139825, 3billion database) and observed to be in trans with another pathogenic variant in this gene (PMID: 15070423, 18941476, 24123366, 9139825). It has been reported with an extremely low frequency in the gnomAD v2.1.1 (https://gnomad.broadinstitute.org/) dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. -
Pathogenic, criteria provided, single submitterresearchUAEU Genomics Laboratory, United Arab Emirates UniversityMay 01, 2022The stop gained NM_004004.6(GJB2):c.71G>A (p.Trp24Ter) variant is an established pathogenic variant reviewed by Clingen hearing Loss expert panel (PMID: 30311386). This variant is one of the common pathogenic variants reported in literature ((PubMed: 9139825, PubMed: 15070423, PubMed: 16088916, PubMed: 31827275, PMID: 30303587), associated with autosomal recessive hearing loss especially in Indian population (PMID: 12833397, PMID: 33614373), with consistent clinical data supporting for pathogenicity. This variant is observed in 134/30616 (0.4377%) alleles from individuals of gnomAD South Asian background in the gnomAD database, which is higher than expected for the disorder, but the evidence for the pathogenicity of this variant for nonsyndromic hearing loss has been determined to outweigh the high allele frequency for classification. The p.Trp24Ter variant in GJB2 is predicted to cause a premature stop codon in the only exon of GJB2 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism . This variant has been detected in patients with hearing loss in trans with pathogenic or suspected-pathogenic variants (PMID: 15070423, 24123366, 18941476, 9139825). Functional studies using a knock-in mouse model demonstrated that the p.Trp24Ter variant leads to the phenotype (PMID:18941476). For these reasons, this variant has been classified as Pathogenic. -
not provided Pathogenic:9
Pathogenic, criteria provided, single submitterclinical testingGeneDxApr 27, 2020Nonsense variant predicted to result in protein truncation, as the last 203 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014) Classified as pathogenic by the ClinGen Hearing Loss Variant Curation Expert Panel (SCV000840546.3; Oza et al., 2018) This variant is associated with the following publications: (PMID: 31160754, 32847582, 31980526, 31827275, 33111345, 26689913, 18294064, 18941476, 29907799, 30394532, 30168495, 29086887, 29542069, 30094485, 15113126, 14985372, 11968091, 12746422, 16380907, 25636251, 26850479, 26778469, 26059209, 25999548, 9139825, 24840842, 24123366, 22975760, 15070423, 16088916, 12833397) -
Pathogenic, criteria provided, single submitterclinical testingInvitaeNov 01, 2022This sequence change creates a premature translational stop signal (p.Trp24*) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 203 amino acid(s) of the GJB2 protein. This variant is present in population databases (rs104894396, gnomAD 0.4%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with autosomal recessive deafness in several families and to be a common cause of the disease in many populations (PMID: 12833397, 15146474, 16088916, 24840842, 26059209). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17002). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GJB2 function (PMID: 18941476). For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesApr 01, 2021The GJB2 c.71G>A; p.Trp24Ter variant (rs104894396) is a common pathogenic variant reported in association with autosomal recessive hearing loss. In a large multi-center North American cohort it accounted for 1.41% of pathogenic variants identified in GJB2 (33 out of 2,341 variants) (Putcha 2007). This variant is also reported in ClinVar (Variation ID: 17002). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Putcha et al. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genet Med. 2007 Jul;9(7):413-26. -
Pathogenic, criteria provided, single submitterclinical testingAthena Diagnostics IncApr 23, 2019The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity. -
Pathogenic, criteria provided, single submitterclinical testingPerkinElmer GenomicsOct 03, 2022- -
Pathogenic, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jul 19, 2016- -
Pathogenic, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2023Criteria applied: PVS1, PP1, PS4 -
Pathogenic, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Pathogenic, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Hearing impairment Pathogenic:4
Likely pathogenic, no assertion criteria providedresearchUniversity of Washington Center for Mendelian Genomics, University of Washington-- -
Pathogenic, no assertion criteria providedresearchCenter for Statistical Genetics, Columbia UniversityNov 22, 2018- -
Pathogenic, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Pathogenic, criteria provided, single submitterclinical testingDepartment of Otolaryngology – Head & Neck Surgery, Cochlear Implant CenterApr 12, 2021PVS1_Strong, PS3_Moderate, PM2_Moderate, PP1_Supporting -
Autosomal dominant nonsyndromic hearing loss 3A Pathogenic:2Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Pathogenic, criteria provided, single submitterclinical testingCounsylDec 18, 2015- -
Pathogenic, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaJan 01, 2016This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PM3,PM4,PP3,PS1,PP4. -
Nonsyndromic genetic hearing loss Pathogenic:1
Pathogenic, reviewed by expert panelcurationClinGen Hearing Loss Variant Curation Expert PanelSep 17, 2018The filtering allele frequency of the p.Trp24X variant in the GJB2 gene is 0.38% (137/ 30782) of South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). However, the ClinGen Hearing Loss Expert Panel believes that the evidence for the pathogenicity of this variant for nonsyndromic hearing loss outweighs the high allele frequency of the variant in population databases. Therefore, the BS1 code will not contribute to the overall classification. The p.Trp24X variant in GJB2 is predicted to cause a premature stop codon in the only exon of GJB2 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). This variant has been detected in patients with hearing loss in trans with at least 4 pathogenic or suspected-pathogenic variants (PM3_VS; PMID: 15070423, 24123366, 18941476, 9139825). A knock-in mouse model demonstrates that the p.Trp24X variant leads to the phenotype (PS3; PMID:18941476). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PVS1, PM3_VS, PS3, BS1. -
Hearing loss Pathogenic:1
Pathogenic, no assertion criteria providedclinical testingClinical Molecular Genetics Laboratory, Johns Hopkins All Children's HospitalOct 27, 2014- -
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 25, 2008The Trp24X variant in GJB2 is a known pathogenic variant and has been reported i n many individuals affected with hearing loss (Kelsell 1997, Roux 2004, Mani 200 9). ACMG/AMP Criteria applied: PVS1, PM3_VeryStrong. -
Hearing loss, autosomal recessive Pathogenic:1
Likely pathogenic, no assertion criteria providedresearchUniversity of Washington Center for Mendelian Genomics, University of Washington-- -
Mutilating keratoderma Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingMendelicsMay 04, 2022- -
Autosomal dominant keratitis-ichthyosis-hearing loss syndrome;C0265964:Mutilating keratoderma;C0266004:Knuckle pads, deafness AND leukonychia syndrome;C1835672:Palmoplantar keratoderma-deafness syndrome;C1844678:X-linked mixed hearing loss with perilymphatic gusher;C1865234:Ichthyosis, hystrix-like, with hearing loss;C2673759:Autosomal recessive nonsyndromic hearing loss 1A;C2675750:Autosomal dominant nonsyndromic hearing loss 3A Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsDec 07, 2021- -
Autosomal recessive nonsyndromic hearing loss 1A;C2675235:Autosomal recessive nonsyndromic hearing loss 1B Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingBaylor Genetics-- -
Ichthyosis, hystrix-like, with hearing loss Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.57
Cadd
Pathogenic
41
Dann
Uncertain
0.99
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.97
D
MutationTaster
Benign
1.0
A;A
Vest4
0.87
GERP RS
5.2

Splicing

Find out SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104894396; hg19: chr13-20763650;