rs2347794

Variant names:

• chr2-47429662-G-A
• rs2347794
• NM_000251.3:c.1077-80G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-47429662-G-A
• chr2-47429662-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000251.3(MSH2):​c.1077-80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,203,188 control chromosomes in the GnomAD database, including 120,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23211 hom., cov: 32)
  • Exomes 𝑓: 0.42 (97607 hom.)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign reviewed by expert panel B:5
• Conservation: PhyloP100: 0.254
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet
• Lynch syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• Muir-Torre syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
• mismatch repair cancer syndrome 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• mismatch repair cancer syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• ovarian cancer

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• malignant pancreatic neoplasm

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• prostate cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-47429662-G-A is Benign according to our data. Variant chr2-47429662-G-A is described in ClinVar as Benign. ClinVar VariationId is 36564.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1077-80G>A		intron_variant	Intron 6 of 15	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1077-80G>A		intron_variant	Intron 6 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79904 AN: 151880 Hom.: 23165 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.421 AC: 442800 AN: 1051188 Hom.: 97607 AF XY: 0.421 AC XY: 224204 AN XY: 531976

African (AFR) AF: 0.788 AC: 18953 AN: 24060

American (AMR) AF: 0.369 AC: 12271 AN: 33224

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 8527 AN: 22574

East Asian (EAS) AF: 0.622 AC: 20946 AN: 33686

South Asian (SAS) AF: 0.472 AC: 31864 AN: 67476

European-Finnish (FIN) AF: 0.531 AC: 25085 AN: 47250

Middle Eastern (MID) AF: 0.424 AC: 1500 AN: 3536

European-Non Finnish (NFE) AF: 0.392 AC: 302846 AN: 773496

Other (OTH) AF: 0.453 AC: 20808 AN: 45886

GnomAD4 genome AF: 0.526 AC: 80007 AN: 152000 Hom.: 23211 Cov.: 32 AF XY: 0.529 AC XY: 39308 AN XY: 74294

African (AFR) AF: 0.773 AC: 32055 AN: 41486

American (AMR) AF: 0.416 AC: 6342 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1280 AN: 3462

East Asian (EAS) AF: 0.676 AC: 3496 AN: 5174

South Asian (SAS) AF: 0.473 AC: 2276 AN: 4814

European-Finnish (FIN) AF: 0.532 AC: 5606 AN: 10542

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27314 AN: 67958

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.520 Hom.: 12068

Bravo AF: 0.527

Asia WGS AF: 0.575 AC: 2001 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:2

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >1% -

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing;curation

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lynch syndrome 1 Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.66
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2347794; hg19: chr2-47656801; COSMIC: COSV51885809;