2-47408504-T-G

Position:

• chr2-47408504-T-G

Variant summary

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

The NM_000251.3(MSH2):​c.315T>G​(p.Asn105Lys) 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. N105S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MSH2 NM_000251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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.315T>G	p.Asn105Lys	missense_variant	2/16	ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.315T>G	p.Asn105Lys	missense_variant	2/16	1	NM_000251.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Uncertain	0.62	D;T;.;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.93
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.0	M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D;D;D;.;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.012	D;T;D;.;D
Sift4G	Benign	0.30	T;T;T;.;T
Polyphen		0.44	B;.;.;.;D
Vest4		0.89
MutPred		0.60		Loss of ubiquitination at K110 (P = 0.0384);.;.;Loss of ubiquitination at K110 (P = 0.0384);Loss of ubiquitination at K110 (P = 0.0384);
MVP		0.80
MPC		0.012
ClinPred		0.95	D
GERP RS		-3.0
Varity_R		0.75
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr2-47635643;