2-47453034-G-A

Position:

• chr2-47453034-G-A

Variant summary

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

The NM_000251.3(MSH2):​c.1386+7377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,968 control chromosomes in the GnomAD database, including 23,430 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 (23430 hom., cov: 31)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3	c.1386+7377G>A		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1386+7377G>A		intron_variant		1	NM_000251.3	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80090 AN: 151848 Hom.: 23383 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.528 AC: 80195 AN: 151968 Hom.: 23430 Cov.: 31 AF XY: 0.530 AC XY: 39391 AN XY: 74268

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.486

Alfa AF: 0.504 Hom.: 2924

Bravo AF: 0.529

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.86
DANN	Benign	0.80

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: rs3771276; hg19: chr2-47680173;