rs63750558

chr2-47429785-C-Achr2-47429785-C-Gchr2-47429785-C-T

Variant summary

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

The NM_000251.3(MSH2):c.1120C>A(p.Gln374Lys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q374H) 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: 5.32

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.1120C>A	p.Gln374Lys	missense_variant	7/16	ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7	c.1120C>A	p.Gln374Lys	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	0.18
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D;.;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D;.;D
REVEL	Uncertain	0.50
Sift	Benign	0.063	T;T;.;T
Sift4G	Benign	0.14	T;T;.;T
Polyphen		0.0030	B;.;.;B
Vest4		0.61
MutPred		0.49		Gain of ubiquitination at Q374 (P = 0.0192);.;Gain of ubiquitination at Q374 (P = 0.0192);Gain of ubiquitination at Q374 (P = 0.0192);
MVP		0.93
MPC		0.0061
ClinPred		0.73	D
GERP RS		5.6
Varity_R		0.81
gMVP		0.47

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: chr2-47656924;