rs10495944

Positions:

• chr2-47476151-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000251.3(MSH2):​c.2006-216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,106 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (902 hom., cov: 31)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-47476151-G-A is Benign according to our data. Variant chr2-47476151-G-A is described in ClinVar as [Benign]. Clinvar id is 1292733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH2	NM_000251.3	c.2006-216G>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.2006-216G>A		intron_variant		1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13960 AN: 151988 Hom.: 902 Cov.: 31

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0974

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

GnomAD4 genome AF: 0.0918 AC: 13962 AN: 152106 Hom.: 902 Cov.: 31 AF XY: 0.0902 AC XY: 6706 AN XY: 74362

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0525

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0973

Alfa AF: 0.122 Hom.: 604

Bravo AF: 0.0833

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.53

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: rs10495944; hg19: chr2-47703290;