rs3771273

chr2-47431335-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000251.3(MSH2):c.1276+1394A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,924 control chromosomes in the GnomAD database, including 23,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (23653 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3	c.1276+1394A>T		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1276+1394A>T		intron_variant		1	NM_000251.3	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80812 AN: 151806 Hom.: 23606 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.533 AC: 80918 AN: 151924 Hom.: 23653 Cov.: 32 AF XY: 0.535 AC XY: 39698 AN XY: 74238

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.492

Alfa AF: 0.490 Hom.: 2435

Bravo AF: 0.533

Asia WGS AF: 0.581 AC: 2003 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.17
Dann	Benign	0.094

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: rs3771273; hg19: chr2-47658474;