chr7-6003755-G-A
Variant summary
Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000535.7(PMS2):c.288C>T(p.Ala96Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 1,602,532 control chromosomes in the GnomAD database, including 5,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★). Synonymous variant affecting the same amino acid position (i.e. A96A) has been classified as Likely benign.
Frequency
Consequence
NM_000535.7 synonymous
Scores
Clinical Significance
Conservation
Publications
- Lynch syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Lynch syndrome 4Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- mismatch repair cancer syndrome 1Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- mismatch repair cancer syndrome 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- malignant pancreatic neoplasmInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- ovarian cancerInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- Muir-Torre syndromeInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- rhabdomyosarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- breast cancerInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- prostate cancerInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -19 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0473 AC: 7192AN: 152018Hom.: 509 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0804 AC: 19273AN: 239762 AF XY: 0.0819 show subpopulations
GnomAD4 exome AF: 0.0470 AC: 68116AN: 1450394Hom.: 4605 Cov.: 29 AF XY: 0.0498 AC XY: 35930AN XY: 722026 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0473 AC: 7200AN: 152138Hom.: 510 Cov.: 32 AF XY: 0.0526 AC XY: 3913AN XY: 74352 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:6
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Lynch syndrome 4 Benign:4
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
not provided Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as 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. -
Lynch syndrome Benign:1
MAF >1% -
Hereditary nonpolyposis colorectal neoplasms Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at