GeneBe

2-47476399-CGA-AGG

Variant names:
GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.
+2 Uncertain · Warm
-7
-6
-1
0
+5
+6
+9
+10
B
LB
VUS
LP
P
 The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_000251.3(MSH2):c.2038_2040delCGAinsAGG (p.681) variant causes a synonymous change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 9.60). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

MSH2
NM_000251.3 synonymous

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60

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: ClinGen, G2P, Orphanet
  • Lynch syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
  • 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: G2P, Labcorp Genetics (formerly Invitae)
  • Muir-Torre syndrome
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • 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

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000251.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

PM2Absent/extremely low in population databases
Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.0005 by highest known P/LP ClinVar AF 0.00268) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000251.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

MSH2 NM_000251.3
MANE Select
HGVSc / HGVSpc.2038_2040delCGAinsAGGp.681
Exon rankN/A
synonymous
Prot: NP_000242.1UniProt: P43246-1
MSH2 NM_001406674.1
HGVSc / HGVSpc.2038_2040delCGAinsAGGp.681
Exon rankN/A
synonymous
Prot: NP_001393603.1
MSH2 NM_001406631.1
HGVSc / HGVSpc.2038_2040delCGAinsAGGp.681
Exon rankN/A
synonymous
Prot: NP_001393560.1

Ensembl Transcripts

MSH2 ENST00000233146.7
TSL:1MANE Select
HGVSc / HGVSpc.2038_2040delCGAinsAGGp.681
Exon rankN/A
synonymous
Prot: ENSP00000233146.2UniProt: P43246-1
MSH2 ENST00000406134.5
TSL:1
HGVSc / HGVSpc.2038_2040delCGAinsAGGp.681
Exon rankN/A
synonymous
Prot: ENSP00000384199.1UniProt: E9PHA6
MSH2 ENST00000918107.1
HGVSc / HGVSpc.2089_2091delCGAinsAGGp.698
Exon rankN/A
synonymous
Prot: ENSP00000588166.1UniProt: A0ACI8SWY1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)
Rare (AF ≤ 0.0001 / Hom ≤ 1)
Global population databases 2 sources
GnomAD3 genomes
Cov:32
GnomAD4 genome
Cov:32
Showing 2 sources
Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

PhyloP100
Pathogenic9.6
Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

Other links and lift over

hg19: chr2-47703538;
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.