rs780178752

Variant names:

• chr2-47403350-C-G
• rs780178752
• NM_000251.3:c.159C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-47403350-C-G
• chr2-47403350-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000251.3(MSH2):​c.159C>G​(p.Ala53Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A53A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MSH2 NM_000251.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 2-47403350-C-G is Benign according to our data. Variant chr2-47403350-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2134375.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.159C>G	p.Ala53Ala	synonymous_variant	Exon 1 of 16	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.159C>G	p.Ala53Ala	synonymous_variant	Exon 1 of 16	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455742 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723696

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33442

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 43930

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25828

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39500

Gnomad4 SAS exome AF: 0.0000118 AC: 1 AN: 84914

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 51870

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1110632

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60134

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary nonpolyposis colorectal neoplasms Benign:1

May 05, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.87
Mutation Taster		=97/3	polymorphism

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: rs780178752; hg19: chr2-47630489;