chr2-47482565-T-C

Variant names:

• chr2-47482565-T-C
• rs2042649
• NM_000251.3:c.2635-214T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000251.3(MSH2):​c.2635-214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,184 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.10 (1477 hom., cov: 32)
• Consequence: MSH2 NM_000251.3 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: -0.0660
• Publications: 16 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-47482565-T-C is Benign according to our data. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47482565-T-C is described in CliVar as Benign. Clinvar id is 91024.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3	c.2635-214T>C		intron_variant	Intron 15 of 15	ENST00000233146.7	NP_000242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7	c.2635-214T>C		intron_variant	Intron 15 of 15	1	NM_000251.3	ENSP00000233146.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15443 AN: 152064 Hom.: 1482 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15438 AN: 152184 Hom.: 1477 Cov.: 32 AF XY: 0.107 AC XY: 7977 AN XY: 74396

African (AFR) AF: 0.0256 AC: 1062 AN: 41526

American (AMR) AF: 0.167 AC: 2560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2622 AN: 5172

South Asian (SAS) AF: 0.157 AC: 760 AN: 4828

European-Finnish (FIN) AF: 0.0995 AC: 1054 AN: 10592

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6810 AN: 67994

Other (OTH) AF: 0.102 AC: 215 AN: 2110

Alfa AF: 0.101 Hom.: 490

Bravo AF: 0.102

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

Submissions by phenotype

Lynch syndrome Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: research

MAF >1% -

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2042649; hg19: chr2-47709704;