rs6726691

Positions:

• chr2-47443165-G-C
• chr2-47443165-G-T

Variant summary

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

The NM_000251.3(MSH2):​c.1277-2383G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,970 control chromosomes in the GnomAD database, including 10,974 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 0.36 (10974 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3	c.1277-2383G>C		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1277-2383G>C		intron_variant		1	NM_000251.3	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55076 AN: 151852 Hom.: 10970 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.363 AC: 55116 AN: 151970 Hom.: 10974 Cov.: 32 AF XY: 0.367 AC XY: 27263 AN XY: 74314

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.328

Alfa AF: 0.188 Hom.: 370

Bravo AF: 0.363

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.81

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: rs6726691; hg19: chr2-47670304;