rs770201760

Positions:

• chr2-47429779-T-A
• chr2-47429779-T-C
• chr2-47429779-T-G

Variant summary

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

The NM_000251.3(MSH2):​c.1114T>A​(p.Leu372Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L372V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MSH2 NM_000251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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/exons	MANE	UniProt
MSH2	NM_000251.3	c.1114T>A	p.Leu372Met	missense_variant	7/16	ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1114T>A	p.Leu372Met	missense_variant	7/16	1	NM_000251.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.0022
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Uncertain	0.68	D
MutationAssessor	Uncertain	2.6	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;N;.;N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.029	D;D;.;D
Sift4G	Uncertain	0.038	D;D;.;D
Polyphen		0.85	P;.;.;D
Vest4		0.72
MutPred		0.62		Gain of disorder (P = 0.1279);.;Gain of disorder (P = 0.1279);Gain of disorder (P = 0.1279);
MVP		0.87
MPC		0.034
ClinPred		0.96	D
GERP RS		-3.6
Varity_R		0.90
gMVP		0.35

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: chr2-47656918;