Variant chr2-47414420-TAAAAAAAAAAAAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000233146.7(MSH2):c.942+3_942+15delAAAAAAAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00439 in 1,044,430 control chromosomes in the GnomAD database, including 107 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 101 hom., cov: 0)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

MSH2
ENST00000233146.7 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 6.75

Variant links:

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-47414420-TAAAAAAAAAAAAA-T is Benign according to our data. Variant chr2-47414420-TAAAAAAAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 182601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414420-TAAAAAAAAAAAAA-T is described in Lovd as [Benign]. Variant chr2-47414420-TAAAAAAAAAAAAA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3 link	c.942+17_942+29delAAAAAAAAAAAAA		intron_variant	Intron 5 of 15	ENST00000233146.7	NP_000242.1	P43246-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 link	c.942+3_942+15delAAAAAAAAAAAAA		splice_region_variant, intron_variant	Intron 5 of 15	1	NM_000251.3	ENSP00000233146.2		P43246-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

2482

AN:

62390

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.000311

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0124

AC:

648

AN:

52420

Hom.:

AF XY:

0.00933

AC XY:

262

AN XY:

28096

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.00595

Gnomad ASJ exome

AF:

0.000801

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000639

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00214

AC:

2102

AN:

982034

Hom.:

AF XY:

0.00187

AC XY:

915

AN XY:

488080

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.0000423

Gnomad4 SAS exome

AF:

0.000592

Gnomad4 FIN exome

AF:

0.000140

Gnomad4 NFE exome

AF:

0.0000676

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.0398

AC:

2485

AN:

62396

Hom.:

101

Cov.:

AF XY:

0.0424

AC XY:

1173

AN XY:

27654

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000311

Gnomad4 OTH

AF:

0.0244

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:5

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Mar 28, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2014	The variant is found in HEREDICANCER,COLYNCH-HEREDIC panel(s). -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Jun 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	May 16, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Mar 18, 2017	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Mar 04, 2025	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Nov 14, 2016	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Breast and/or ovarian cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 01, 2022

- -

Lynch syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Sep 24, 2015

- -

Hereditary nonpolyposis colorectal neoplasms

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over