chr2-47445572-C-A

Variant names:

• chr2-47445572-C-A
• NM_000251.3:c.1301C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000251.3(MSH2):​c.1301C>A​(p.Ala434Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MSH2 NM_000251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.1301C>A	p.Ala434Glu	missense_variant	Exon 8 of 16	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1301C>A	p.Ala434Glu	missense_variant	Exon 8 of 16	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Benign	19
DANN	Benign	0.75
DEOGEN2	Benign	0.34	T;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.054
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.93	L;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.60	N;N;.;N
REVEL	Uncertain	0.56
Sift	Benign	0.88	T;T;.;T
Sift4G	Benign	1.0	T;T;.;T
Polyphen		0.12	B;.;.;B
Vest4		0.67
MutPred		0.52		Gain of disorder (P = 0.0674);.;Gain of disorder (P = 0.0674);Gain of disorder (P = 0.0674);
MVP		0.93
MPC		0.0063
ClinPred		0.72	D
GERP RS		5.4
Varity_R		0.38
gMVP		0.62

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: chr2-47672711;