rs2347794

Positions:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000233146.7(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 ENST00000233146.7 intron
• Clinical Significance: Benign reviewed by expert panel B:5
• Conservation: PhyloP100: 0.254

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 36564.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47429662-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1077-80G>A		intron_variant		ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1077-80G>A		intron_variant		1	NM_000251.3	ENSP00000233146	P1

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

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.622

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.453

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

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.487

Alfa AF: 0.452 Hom.: 4838

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

Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, reviewed by expert panel	research	International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	Sep 05, 2013	MAF >1% -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Lynch syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.66

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