2-47466769-C-G

Position:

• chr2-47466769-C-G

Variant summary

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

The NM_000251.3(MSH2):​c.1622C>G​(p.Thr541Ser) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MSH2 NM_000251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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]

MSH2 (HGNC:):

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	Protein	UniProt
MSH2	NM_000251.3	c.1622C>G	p.Thr541Ser	missense_variant	10/16	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.1622C>G	p.Thr541Ser	missense_variant	10/16	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;.;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.022	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N;.;N
REVEL	Uncertain	0.54
Sift	Benign	0.13	T;T;.;T
Sift4G	Benign	0.39	T;T;.;T
Polyphen		0.51	P;.;.;P
Vest4		0.52
MutPred		0.49		Gain of disorder (P = 0.0421);.;Gain of disorder (P = 0.0421);Gain of disorder (P = 0.0421);
MVP		0.87
MPC		0.022
ClinPred		0.94	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.62
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr2-47693908;