NM_000251.3:c.939T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000251.3(MSH2):c.939T>C(p.Phe313Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSH2
NM_000251.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.256

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

Lynch syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet
Lynch syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
Muir-Torre syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
mismatch repair cancer syndrome 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
mismatch repair cancer syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
ovarian cancer
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
malignant pancreatic neoplasm
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
rhabdomyosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MSH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 2-47414415-T-C is Benign according to our data. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47414415-T-C is described in CliVar as Likely_benign. Clinvar id is 525943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.256 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3 link	c.939T>C	p.Phe313Phe	synonymous_variant	Exon 5 of 16	ENST00000233146.7	NP_000242.1	P43246-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 link	c.939T>C	p.Phe313Phe	synonymous_variant	Exon 5 of 16	1	NM_000251.3	ENSP00000233146.2		P43246-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116892

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1401440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696856

African (AFR)

AF:

0.00

AC:

AN:

30158

American (AMR)

AF:

0.00

AC:

AN:

34648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24386

East Asian (EAS)

AF:

0.00

AC:

AN:

38744

South Asian (SAS)

AF:

0.00

AC:

AN:

77542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084988

Other (OTH)

AF:

0.00

AC:

AN:

57334

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

116892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55956

African (AFR)

AF:

0.00

AC:

AN:

29672

American (AMR)

AF:

0.00

AC:

AN:

10830

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3012

East Asian (EAS)

AF:

0.00

AC:

AN:

4340

South Asian (SAS)

AF:

0.00

AC:

AN:

3126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56762

Other (OTH)

AF:

0.00

AC:

AN:

1386

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

May 05, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary nonpolyposis colorectal neoplasms

Benign:1

Mar 12, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Jul 17, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

(source)

DANN

Benign

0.71

PhyloP100

0.26

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over