13-32363369-G-C

Position:

• chr13-32363369-G-C

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM5 PP3_Strong PP5_Very_Strong

The NM_000059.4(BRCA2):​c.8167G>C​(p.Asp2723His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2723G) has been classified as Pathogenic.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: BRCA2 NM_000059.4 missense
• Clinical Significance: Pathogenic reviewed by expert panel P:29 U:1
• Conservation: PhyloP100: 9.60

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Pathogenic. Variant got 14 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr13-32363370-A-G is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987
• PP5: Variant 13-32363369-G-C is Pathogenic according to our data. Variant chr13-32363369-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 52515.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32363369-G-C is described in Lovd as [Likely_pathogenic]. Variant chr13-32363369-G-C is described in Lovd as [Pathogenic]. Variant chr13-32363369-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.8167G>C	p.Asp2723His	missense_variant	18/27	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.8167G>C	p.Asp2723His	missense_variant	18/27	5	NM_000059.4	ENSP00000369497	A2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74328

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:29 Uncertain:1

Revision: reviewed by expert panel

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2 Pathogenic:8 Uncertain:1

Pathogenic, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Jul 08, 2023	This missense variant replaces aspartic acid with histidine at codon 2723 in the DNA binding domain of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant causes the mislocalization of BRCA2 to the cytoplasm (PMID: 15695382, 18607349, 24013206) and disrupts BRCA2 function, including homology-directed DNA repair activity (PMID: 15695382, 18607349, 19043619, 23108138, 25146914). This variant has been reported in over a dozen individuals affected with breast and/or ovarian cancer (PMID: PMID: 11207042, 23961350, 24052750, 24728189, 33471991; Leiden Open Variation Database DB-ID BRCA2_000290) and with prostate cancer (PMID: 23569316). Multifactorial analyses based on numerous individuals' personal and family history of cancer and tumor pathology have determined this variant to be disease-causing (PMID: 15290653, 16489001, 18451181, 25085752). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different missense variant at the same codon, p.Asp2723Gly, is known to be pathogenic (Clinvar variation ID: 38141), indicating that arginine at this position is important for BRCA2 function. Based on the available evidence, this variant is classified as Pathogenic. -
Uncertain significance, no assertion criteria provided	clinical testing	Breast Cancer Information Core (BIC) (BRCA2)	May 29, 2002	- -
Pathogenic, criteria provided, single submitter	clinical testing	Counsyl	Nov 11, 2016	- -
Pathogenic, no assertion criteria provided	clinical testing	Sharing Clinical Reports Project (SCRP)	May 01, 2012	- -
Pathogenic, reviewed by expert panel	curation	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	Aug 10, 2015	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 1 -
Pathogenic, criteria provided, single submitter	clinical testing	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	Oct 02, 2015	- -
Pathogenic, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 08, 2014	- -
Pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Pathogenic, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Pathogenic:6

Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2023	Observed in individuals with personal and family history of BRCA-related cancers, segregating with disease in at least 10 families (Pages et al., 2001; Goldgar et al., 2004; Mitra et al., 2008; Solano et al., 2012; Song et al., 2014; Shimelis et al., 2017); Published functional studies demonstrate a damaging effect: aberrant cellular localization, inability to rescue cell growth, and defective homology-directed repair activity (Wu et al., 2005; Farrugia et al., 2008; Kuznetsov et al., 2008; Jeyasekharan et al., 2013; Guidugli et al., 2018; Hart et al., 2019); Multifactorial studies suggest this variant is associated with breast and ovarian cancer (Lindor et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 8395G>C; This variant is associated with the following publications: (PMID: 24728189, 15695382, 18451181, 18182994, 25447315, 23961350, 25085752, 11207042, 15026808, 29922827, 28888541, 21702907, 22505045, 24323938, 25146914, 25782689, 24013206, 15290653, 19043619, 23108138, 18607349, 16489001, 27225637, 20223037, 26775038, 28283652, 28324225, 26586665, 28008555, 27550963, 26681312, 28158555, 29394989, 29446198, 29988080, 30322717, 30309722, 31263054, 32444794, 30696104, 34399810, 33609447, 30787465, 28184943, 35736817, 35464868, 12228710, 29884841, 33964450, 21990134, 35665744) -
Pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Dec 06, 2019	In the published literature, this variant has been reported in individuals with breast, ovarian, and prostate cancer (PMIDs: 18182994 (2008), 18451181 (2008), 19043619 (2008), 16489001 (2006)), and to segregate with breast and/or ovarian cancer in multiple families (PMIDs: 16489001 (2006), 15290653 (2004)). In addition, this variant has been reported to have a deleterious effect on BRCA2 protein function in numerous studies (PMIDs: 29394989 (2018), 25146914 (2014), 19043619 (2008), 16978908 (2007), 15695382 (2005)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	BRCA2: PM1:Strong, PS3, PM2, PP1, PS4:Supporting, BP1 -
Pathogenic, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 08, 2023	The BRCA2 c.8167G>C; p.Asp2723His variant (rs41293511), is reported in the literature in several individuals affected with breast and ovarian cancer (Goldgar 2004, Pages 2001, Wu 2005). Functional analyses of BRCA2 protein carrying this variant demonstrate centrosome amplification and aberrant subcellular localization resulting in defective DNA repair on exposure to gamma irradiation and mitomycin-c (Carvalho 2007, Goldgar 2004, Wu 2005). Furthermore, BRCA2 Asp2723His variant has been shown to interfere with the nuclear localization of RAD51, another key DNA repair protein (Jeyasekharan 2013). This variant is reported as pathogenic by several laboratories in ClinVar (Variation ID: 52515). It is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.932). Several alternative changes at this amino acid location (p.Asp2723Gly, p.Asp2723Ala, p.Asp2723Val) that are predicted to be pathogenic have also been reported in patients with breast and ovarian cancer (Guidugli 2018). Based on available information, the p.Asp2723His variant is considered to be pathogenic. References: Carvalho MA et al. Functional assays for BRCA1 and BRCA2. Int J Biochem Cell Biol. 2007;39(2):298-310. Goldgar DE et al. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet. 2004 Oct;75(4):535-44. Guidugli L et al. Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches. Am J Hum Genet. 2018 Feb 1;102(2):233-248. Jeyasekharan AD et al. A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. Nat Struct Mol Biol. 2013 Oct;20(10):1191-8. Pages S et al. Screening of male breast cancer and of breast-ovarian cancer families for BRCA2 mutations using large bifluorescent amplicons. Br J Cancer. 2001 Feb;84(4):482-8. Wu K et al. Functional evaluation and cancer risk assessment of BRCA2 unclassified variants. Cancer Res. 2005 Jan 15;65(2):417-26. -
Pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Nov 29, 2022	- -

Hereditary breast ovarian cancer syndrome Pathogenic:6

Pathogenic, criteria provided, single submitter	clinical testing	National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	Nov 16, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 2723 of the BRCA2 protein (p.Asp2723His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and ovarian cancer (PMID: 11207042, 15290653, 16489001, 23961350, 24728189). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 52515). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) indicates that this missense variant is expected to disrupt BRCA2 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA2 function (PMID: 15695382, 18607349, 23108138, 24013206, 25146914). This variant disrupts the p.Asp2723 amino acid residue in BRCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21990134). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, no assertion criteria provided	research	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	Jan 31, 2014	- -
Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 09, 2016	Variant summary: The BRCA2 c.8167G>C (p.Asp2723His) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was absent in 121762 control chromosomes. This variant is a recurrent pathogenic mutation reported in literature and clinical databases with consistent patient and functional data, including support from multifactorial probability model and reported co-segregation with disease. In addition, several clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Therefore, this variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 12, 2020	The p.Asp2723His variant in BRCA2 has been identified in >20 individuals with BRCA2-associated cancers and segregated with disease with multiple individuals from many families (Pages 2001 PMID: 11207042, Goldgar 2004 PMID: 15290653, Chenevix-Trench 2006 PMID: 16489001, Solano 2012 PMID: 23961350, Song 2014 PMID: 24728189). This variant was absent from large population studies. In vitro and in vivo functional studies support an impact on protein function (Chenevix-Trench 2006 PMID: 16489001, Wu 2005 PMID: 15695382, Farrugia 2008 PMID: 18451181, Kuznetsov 2008 PMID: 18607349, Jeyasekharan 2013 PMID: 24013206, Guidugli 2018 PMID: 29394989) and computational prediction tools and conservation analysis are consistent with pathogenicity. Moreover, this variant as well as another variant involving this codon (p.Asp2723Gly) have been classified as pathogenic on August 10, 2015 by the ClinGen-approved ENIGMA expert panel (SCV000244481.1). Multiple other variants involving this codon have also been identified in individuals with HBOC (ClinVar, HGMD: Stenson 2017). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast and ovarian cancer (HBOC). ACMG/AMP Criteria applied: PS4, PS3_Supporting, PP1_Moderate, PM2, PM5, PP3. -
Pathogenic, no assertion criteria provided	clinical testing	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	Sep 27, 2021	- -

Familial cancer of breast Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Nov 29, 2024	Criteria applied: PS3,PP4_STR,PP1_MOD,PP3 -
Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Mar 12, 2024	- -

Hereditary cancer-predisposing syndrome Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Ambry Genetics	Apr 07, 2022	The p.D2723H pathogenic mutation (also known as c.8167G>C), located in coding exon 17 of the BRCA2 gene, results from a G to C substitution at nucleotide position 8167. The aspartic acid at codon 2723 is replaced by histidine, an amino acid with some similar properties. This alteration has been classified as pathogenic (p>0.99) by multifactorial analysis, which integrates the following lines of evidence to produce a quantitative likelihood of pathogenicity: in silico prediction models, segregation with disease, tumor characteristics, and mutation co-occurrence (Goldgar DE et al. Am. J. Hum. Genet. 2004 Oct;75:535-44; Easton DF et al. Am. J. Hum. Genet. 2007 Nov;81:873-83; Tavtigian SV et al. Hum. Mutat. 2008 Nov;29:1342-54; Karchin R et al. Cancer Inform. 2008 Apr;6:203-16; Lindor NM et al. Hum. Mutat. 2012 Jan;33:8-21; Vallee MP et al. Hum. Mutat. 2012 Jan;33:22-8). Moreover, functional studies have shown that this alteration affects the DNA repair function of BRCA2 (Wu K et al. Cancer Res. 2005 Jan;65:417-26; Farrugia DJ et al. Cancer Res. 2008 May;68:3523-31; Kuznetsov SG et al. Nat. Med. 2008 Aug;14:875–881; Guidugli L et al. Cancer Res. 2013 Jan;73:265-75; Guidugli L et al. Am. J. Hum. Genet. 2018 Feb;102:233-248). Additionally, this alteration has been detected in multiple hereditary breast and ovarian cancer families, including families with male breast cancer (Pages S et al. Br. J. Cancer. 2001 Feb;84:482-8; Goldgar DE et al. Am. J. Hum. Genet. 2004 Oct;75:535-44; Wu K et al. Cancer Res. 2005 Jan;65:417-26; Solano AR et al. Springerplus. 2012 Sep;1:20; Meisel C et al. Arch. Gynecol. Obstet. 2017 May;295:1227-1238). Of note, this alteration is also designated as 8395G>C in published literature. Based on the available evidence, this alteration is classified as a pathogenic mutation. -
Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Dec 05, 2022	This missense variant replaces aspartic acid with histidine at codon 2723 in the DNA binding domain of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant causes the mislocalization of BRCA2 to the cytoplasm (PMID: 15695382, 18607349, 24013206) and disrupts BRCA2 function, including homology-directed DNA repair activity (PMID: 15695382, 18607349, 19043619, 23108138, 25146914). This variant has been reported in over a dozen individuals affected with breast and/or ovarian cancer (PMID: PMID: 11207042, 23961350, 24052750, 24728189, 33471991; Leiden Open Variation Database DB-ID BRCA2_000290) and with prostate cancer (PMID: 23569316). Multifactorial analyses based on numerous individuals' personal and family history of cancer and tumor pathology have determined this variant to be disease-causing (PMID: 15290653, 16489001, 18451181, 25085752). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different missense variant at the same codon, p.Asp2723Gly, is known to be pathogenic (Clinvar variation ID: 38141), indicating that arginine at this position is important for BRCA2 function. Based on the available evidence, this variant is classified as Pathogenic. -

Medulloblastoma;C0346153:Familial cancer of breast;C0376358:Malignant tumor of prostate;C1838457:Fanconi anemia complementation group D1;C2675520:Breast-ovarian cancer, familial, susceptibility to, 2;C2751641:Glioma susceptibility 3;C3150546:Pancreatic cancer, susceptibility to, 2;CN033288:Wilms tumor 1 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 03, 2021

- -

Breast and/or ovarian cancer Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Jun 29, 2023

- -

Carcinoma of pancreas Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

CZECANCA consortium

Mar 04, 2021

- -

BRCA2-related disorder Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2023

The BRCA2 c.8167G>C variant is predicted to result in the amino acid substitution p.Asp2723His. This variant has been documented in multiple individuals with breast and ovarian cancer and has been shown to cause defective DNA repair (Goldgar et al. 2004. PubMed ID: 15290653; Karchin et al. 2008. PubMed ID: 19043619; Guidugli et al. 2013. PubMed ID: 23108138; Guidugli et al. 2018. PubMed ID: 29394989). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. It is interpreted as pathogenic in ClinVar, including by the ENIGMA expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/52515/). This variant is interpreted as pathogenic. -

Malignant tumor of breast Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

-

The p.Asp2723His variant is identified in the literature in 5 out of 554 proband chromosomes (frequency 0.009) in individuals with breast (male and female), ovarian and prostate cancers, however it is not analyzed in enough control chromosomes to determine the population frequency (0 out of 380, frequency=0) (Chenevix-Trench 2006, Mitra 2008, Pages 2001, Ding 2011). Furthermore, It is listed in dbSNP database as coming from a "clinical source" (ID#: rs41293511) with no frequency information available, and therefore, not informative to assess the frequency of this variant in the general population. The p.Asp2723 residue is conserved in mammals and other species and computational analyses (SIFT, Polyphen2, AlignGVGD) predict deleterious impact on the protein function. In addition, in vitro functional studies shows impaired BRCA2 function (Kuzentsov 2008, Wu 2005, Karchin 2008, Walker 2010, Carvalho_2007) and multifactorial likelihood-ratio models shows higher odds in favor of causality for this variant (Goldgar 2004, Farrugia 2008, Chenevix-Trench 2006). In the UMD database, this variant has been identified as an isolated "pathogenous" variant in 19 individuals with breast or ovarian cancers, increasing the likelihood this variant is clinically important. Other variants at the same location include p.Asp2723Gly (5 times in UMD), p.Asp2723Val (2 times in UMD) and p.Asp2723Glu (1 time). The p.Asp2723Gly has been shown to result in loss of the last 164 nucleotides of exon18, and shown to be deleterious by several studies (Farrugia 2008, Easton 2007, Karchin 2008), increasing the likelihood that an alteration to this residue is pathogenic. In summary, based on the above information, this variant is classified as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	1.1	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N;N
REVEL	Pathogenic	0.93
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.93
MutPred		0.95		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.99
MPC		0.17
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41293511; hg19: chr13-32937506;