17-43106457-T-C

Position:

• chr17-43106457-T-C

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1 PM2 PM5 PP3_Strong PP5_Very_Strong

The NM_007294.4(BRCA1):​c.211A>G​(p.Arg71Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000014 in 1,427,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71K) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BRCA1 NM_007294.4 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Pathogenic reviewed by expert panel P:31 U:1 O:1
• Conservation: PhyloP100: 4.16

Genes affected

BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PM1: In a mutagenesis_site No effect on interaction with BAP1. (size 0) in uniprot entity BRCA1_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_007294.4
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-43106456-C-T is described in Lovd as [Pathogenic].
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 17-43106457-T-C is Pathogenic according to our data. Variant chr17-43106457-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 17693.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43106457-T-C is described in Lovd as [Pathogenic]. Variant chr17-43106457-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA1	NM_007294.4	c.211A>G	p.Arg71Gly	missense_variant, splice_region_variant	4/23	ENST00000357654.9	NP_009225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCA1	ENST00000357654.9	c.211A>G	p.Arg71Gly	missense_variant, splice_region_variant	4/23	1	NM_007294.4	ENSP00000350283	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249744 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134994

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427816 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 711876

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:31 Uncertain:1 Other:1

Revision: reviewed by expert panel

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 1 Pathogenic:12 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 01, 2003	- -
Pathogenic, no assertion criteria provided	clinical testing	Breast Cancer Information Core (BIC) (BRCA1)	May 29, 2002	- -
Pathogenic, criteria provided, single submitter	clinical testing	Genologica Medica	Jan 01, 2017	- -
not provided, no classification provided	in vitro	Brotman Baty Institute, University of Washington	-	- -
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, no assertion criteria provided	clinical testing	Sharing Clinical Reports Project (SCRP)	Oct 15, 2012	- -
Pathogenic, reviewed by expert panel	curation	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	Jun 18, 2019	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 = 0.999388 -
Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Dec 22, 2023	- -
Pathogenic, criteria provided, single submitter	clinical testing	DASA	Mar 05, 2022	Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID 30209399; 11385711; 19123044). - PS3_moderate.The c.211A>G;p.(Arg71Gly) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 17693; PMID: 12014998) - PS4. The variant is present at low allele frequencies population databases (rs80357382 – gnomAD 0.00004004%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID:185705; ClinVar ID:54471; ClinVar ID :267512) - PM5. The variant co-segregated with disease in multiple affected family members (PMID: 12014998; 20215541) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	Jul 22, 2021	ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderate, PM5 moderate, PP1 strong, PP3 supporting -
Pathogenic, criteria provided, single submitter	clinical testing	Counsyl	Mar 16, 2016	- -
Pathogenic, no assertion criteria provided	clinical testing	BRCAlab, Lund University	Mar 02, 2020	- -
Pathogenic, no assertion criteria provided	case-control	Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)	May 24, 2021	- -

Hereditary breast ovarian cancer syndrome Pathogenic:6

Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 27, 2020	Variant summary: BRCA1 c.211A>G (p.Arg71Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. As a variant located within the exonic-splice region close to the intronic splice donor site, several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 5' splicing donor site. Two predict the variant weakens a 5' donor site. At least two publications report experimental evidence that this variant affects mRNA splicing (example, Vega_2001, Santos_2009). The variant allele was found at a frequency of 4e-06 in 249844 control chromosomes. c.211A>G has been widely reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. At-least one mutually exclusive co-occurrence with another pathogenic variant(s) has been reported in the UMD database (BRCA2 c.2701delC, p.Ala902LeufsX2). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a loss of function as evaluated in a high throughput system that used saturation genome editing to assess homology directed repair (HDR) activity (Findlay_2018). Multiple clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014. Some submitters cite overlapping evidence utilized in the context of this evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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	Department of Pathology and Molecular Medicine, Queen's University	Apr 20, 2017	- -
Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	Jul 02, 2018	- -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 71 of the BRCA1 protein (p.Arg71Gly). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs80357382, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast and ovarian cancer (PMID: 12014998, 20215541). It is commonly reported in individuals of Spanish ancestry (PMID: 11385711, 23683081, 27081505). This variant is also known as 330A>G. ClinVar contains an entry for this variant (Variation ID: 17693). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 2316185, 11320250, 16403807, 20103620, 21725363). Studies have shown that this missense change results in activation of a cryptic splice site and exon 4 skipping and introduces a premature termination codon (PMID: 2173504, 11385711, 19123044, 20215541; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	research	Genetics Program, Instituto Nacional de Cancer	Nov 01, 2021	- -

not provided Pathogenic:5 Uncertain:1

Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Feb 07, 2022	Exonic splice variant demonstrated to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease (Vega 2001, Santos 2009); Published functional studies demonstrate a damaging effect: classified as loss of function based on results of a cell survival assay and multifactorial likelihood analysis suggests this variant is pathogenic (Findlay 2018, Parsons 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 330A>G; This variant is associated with the following publications: (PMID: 21725363, 27083775, 28477318, 28664506, 20215541, 23161852, 15235020, 11320250, 10508480, 21735045, 26246475, 25823446, 19123044, 25782689, 26913838, 22505045, 28453507, 28127413, 27081505, 27836010, 30240327, 29884136, 30103829, 20103620, 30209399, 29446198, 11385711, 30995943, 30720243, 30606148, 30630528, 31131967, 31454914, 25525159, 33087888, 31589614, 32341426, 32719484, 33558524, 20104584, 24389207, 27535533) -
Pathogenic, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Sep 18, 2023	The BRCA1 c.211A>G (p.Arg71Gly) variant has been reported in the published literature in multiple individuals with breast cancer and it is described as a founder mutation in the Spanish population (PMIDs: 11385711 (2001) and 20215541 (2010)). In a large-scale breast cancer association study, the variant was observed among the breast cancer cases and not in healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA1)). Published functional studies have shown that this variant has a deleterious effect on BRCA1 mRNA splicing (PMIDs: 11385711 (2001), 20215541 (2010), 21735045 (2012), and 22505045 (2012)). In addition, this variant has been characterized as being pathogenic in a multifactorial likelihood study (PMID: 31131967 (2019)). The frequency of this variant in the general population, 0.000004 (1/249744 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, this variant is classified as pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Feb 17, 2023	- -
Pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Hereditary cancer-predisposing syndrome Pathogenic:3

Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Dec 22, 2022	This variant is located in exon 4 near the intron 4 splice donor site. RNA analyses have shown that this variant results in out-of-frame splicing involving exon 4 that is predicted to cause an absent or non-functional protein product (PMID: 11385711, 20215541, 22505045). This variant has been reported to be loss-of-function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in over 20 individuals and families affected with breast and ovarian cancer (PMID: 10508480, 12955716, 18159056, 19123044, 20104584, 23683081, 25716084, 28664506, 28985766, 29088781, 30606148, 33471991; Leiden Open Variation Database DB-ID BRCA1_000059), and has been identified in 129 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). Haplotype analysis suggests that this variant is a founder mutation originating in Northern Spain (PMID: 11385711, 12014998). This variant has been reported to segregate with disease with a likelihood ratio for pathogenicity of 383.2656 (PMID: 31131967). This variant has been identified in 1/249744 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Ambry Genetics	May 23, 2024	The c.211A>G pathogenic mutation (also known as p.R71G), located in coding exon 3 of the BRCA1 gene, results from an A to G substitution at nucleotide position 211. Also designated as 330A>G in some published literature, this mutation has been described as a founder mutation originating from the Galicia region of North Western Spain and has been reported in numerous breast and ovarian cancer patients and families (Villarreal-Garza C et al. Breast Cancer Res. Treat. 2015 Apr;150:389-94; Janavièius R. EPMA J. 2010 Sep;1:397-412; Diez O et al. Int. J. Cancer. 1999 Nov;83:465-9; Rebbeck TR et al. Breast Cancer Res. 2016 Nov;18(1):112; Alvarez C et al. Oncotarget, 2017 Sep;8:74233-74243; Yang XR et al. Breast Cancer Res. Treat. 2017 Oct;165(3):687-697; Cotrim DP et al. BMC Cancer, 2019 Jan;19:4). Additionally, this mutation has been described in five unrelated families and was observed to result in aberrant splicing (Ambry internal data; Sanz DJ et al. Clin. Cancer Res. 2010 Mar;16:1957-67; Houdayer C et al. Hum. Mutat. 2012 Aug;33:1228-38). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature 2018 10;562(7726):217-222). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the available evidence, this alteration is classified as a disease-causing mutation. -
Pathogenic, criteria provided, single submitter	curation	Sema4, Sema4	Feb 13, 2022	- -

Familial cancer of breast Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Feb 23, 2017	- -
Pathogenic, no assertion criteria provided	research	Center of Medical Genetics and Primary Health Care	Apr 08, 2020	ACMG Guidelines 2015 criteria The BRCA1 variant p.Arg71Gly is a known pathogenic missense mutation in exon 5 that is found in the Zinc finger domain, RING/FYVE/PHD-type (E10-85E aa). It is now recognized to bind DNA, RNA, protein and/or lipid substrates (PMID: 17210253). It is found in a mutational hotspot including 28 pathogenic frameshift and nonsense variants (PM1 Pathogenic Moderate). It was conformed via RT-PCR that this variant results in the loss of 22 nucleotides in exon 5 and a subsequent premature stop codon due to a cryptic splice donor site (PMID: 11385711; 19123044) (PS3 Pathogenic Strong). The allele frequency in GnomAD exomes is 0.000004 which is less the threshold 0.0001 for recessive gene BRCA1, and the variant is not found in GnomAD genomes (PM2 Pathogenic Moderate). Three different pathogenic missense changes at the same amino acid residue (chr17:41258473C>A (Arg71Ile); chr17:41258473C>G (Arg71Thr); chr17:41258473C>T (Arg71Lys)) have been reported in ClinVar (PM5 Pathogenic Moderate). 10 pathogenic predictions from DANN, EIGEN, FATHMM-MKL, M-CAP, MVP, MutationAssessor, MutationTaster, PrimateAI, REVEL and SIFT versus 1 benign prediction from DEOGEN2 support its deleterious effect (PP3 Pathogenic Supporting). The variant has been classified as pathogenic by the ClinGen-approved ENIGMA expert panel (ClinVar SCV001161539.1) (PP5 Pathogenic Supporting). In our study this variant was found in a 36-year-old female with unilateral breast cancer and a family history of breast cancer. Therefore, this variant was classified as a Pathogenic. -

not specified Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 02, 2018

The BRCA1 c.211A>G; p.Arg71Gly variant (rs80357382), also known as 330A>G, has been described in multiple families with history of breast and/or ovarian cancers (Diez 1999, Sanz 2010, Vega 2001). It is reported as pathogenic by several laboratories in ClinVar (Variation ID: 17693), and is only observed on 1 allele in the Genome Aggregation Database. This variant is two nucleotide from the canonical splice site, and computational algorithms (Alamut v.2.11) predict the weakening or loss of the splice donor. Consistent with this, functional characterization of the variant indicates aberrant splicing of the BRCA1 transcript, resulting in the introduction of a premature termination codon (Houdayer 2012, Sanz 2010, Vega 2001). Based on available information, this variant is considered pathogenic. References: Diez O et al. BRCA1 mutation analysis in 83 Spanish breast and breast/ovarian cancer families. Int J Cancer. 1999; 83(4):465-9. Houdayer C et al. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Hum Mutat. 2012; 33(8):1228-38. Sanz D et al. A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. Clin Cancer Res. 2010; 16(6):1957-67. Vega A et al. The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript. Hum Mutat. 2001; 17(6):520-1. -

Familial cancer of breast;C2676676:Breast-ovarian cancer, familial, susceptibility to, 1;C3280442:Pancreatic cancer, susceptibility to, 4;C4554406:Fanconi anemia, complementation group S Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 08, 2021

- -

BRCA1-related disorder Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 03, 2024

The BRCA1 c.211A>G variant is predicted to result in the amino acid substitution p.Arg71Gly. This variant has been reported to be causative for breast/ovarian cancer, and appears to be a Spanish founder variant (Díez et al. 1999. PubMed ID: 10508480; Vega et al. 2002. PubMed ID: 12014998; Sanz et al. 2010. PubMed ID: 20215541; Felix et al. 2014. PubMed ID: 27081505). This variant has been shown in vitro to cause exon skipping by introducing a cryptic splice site (Houdayer et al. 2012. PubMed: 22505045), and cells harboring this variant are more sensitive to radiation and showed genomic instability compared to cells with control variants (Cochran et al. 2015. PubMed: 26246475). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has been reported in ClinVar as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/17693/). This variant is interpreted as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	.;T;.;.;.;.;T;.;.;T;T;T;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Uncertain	2.5	M;M;M;M;.;M;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;D;N;N;.;N;N;D;.
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;.;D;D;D;.
Sift4G	Uncertain	0.060	T;D;D;T;D;T;.;D;D;.;T;T;.;.
Polyphen		0.96, 0.98, 1.0	.;P;.;.;.;D;.;.;D;.;.;.;.;.
Vest4		0.85
MutPred		0.81		Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);.;Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);.;Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);Gain of ubiquitination at K70 (P = 0.0519);.;
MVP		0.94
MPC		0.23
ClinPred		0.87	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.64		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs80357382; hg19: chr17-41258474; COSMIC: COSV58798129; COSMIC: COSV58798129;