rs3771281

Variant names:

• chr2-47465142-C-T
• rs3771281
• NM_000251.3:c.1511-1516C>T

Variant summary

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

The NM_000251.3(MSH2):​c.1511-1516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,978 control chromosomes in the GnomAD database, including 19,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.48 (19456 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: -0.436

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=-1.01).
• BP6: Variant 2-47465142-C-T is Benign according to our data. Variant chr2-47465142-C-T is described in ClinVar as [Benign]. Clinvar id is 90687.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47465142-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1511-1516C>T		intron_variant	Intron 9 of 15	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1511-1516C>T		intron_variant	Intron 9 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73498 AN: 151858 Hom.: 19417 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.484 AC: 73598 AN: 151978 Hom.: 19456 Cov.: 32 AF XY: 0.486 AC XY: 36110 AN XY: 74276

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.451

Alfa AF: 0.405 Hom.: 6870

Bravo AF: 0.485

Asia WGS AF: 0.551 AC: 1913 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.55

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: rs3771281; hg19: chr2-47692281;