2-47410369-A-C

Variant names:

• chr2-47410369-A-C
• NM_000251.3:c.642A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000251.3(MSH2):​c.642A>C​(p.Arg214Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: MSH2 NM_000251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40245563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.642A>C	p.Arg214Ser	missense_variant	Exon 3 of 16	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.642A>C	p.Arg214Ser	missense_variant	Exon 3 of 16	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Uncertain	0.79	D;.;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D;D;.;D
REVEL	Uncertain	0.56
Sift	Benign	0.086	T;T;.;T
Sift4G	Benign	0.13	T;T;.;T
Polyphen		0.056	B;.;.;B
Vest4		0.70
MutPred		0.53		Loss of MoRF binding (P = 0.0308);.;Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);
MVP		0.96
MPC		0.0069
ClinPred		0.45	T
GERP RS		-1.1
Varity_R		0.85
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-47637508;