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.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.1424T>C (p.Val475Ala)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely benign
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000535.7(PMS2):c.1424T>C (p.Val475Ala)
Variation ID: 1772340 Accession: VCV001772340.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5987341 (GRCh38) [ NCBI UCSC ] 7: 6026972 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 29, 2022 May 1, 2024 Mar 30, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.1424T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Val475Ala missense NM_001018040.1:c.1019T>C NP_001018050.1:p.Val340Ala missense NM_001322003.2:c.1019T>C NP_001308932.1:p.Val340Ala missense NM_001322004.2:c.1019T>C NP_001308933.1:p.Val340Ala missense NM_001322005.2:c.1019T>C NP_001308934.1:p.Val340Ala missense NM_001322006.2:c.1268T>C NP_001308935.1:p.Val423Ala missense NM_001322007.2:c.1106T>C NP_001308936.1:p.Val369Ala missense NM_001322008.2:c.1106T>C NP_001308937.1:p.Val369Ala missense NM_001322009.2:c.1019T>C NP_001308938.1:p.Val340Ala missense NM_001322010.2:c.863T>C NP_001308939.1:p.Val288Ala missense NM_001322011.2:c.491T>C NP_001308940.1:p.Val164Ala missense NM_001322012.2:c.491T>C NP_001308941.1:p.Val164Ala missense NM_001322013.2:c.851T>C NP_001308942.1:p.Val284Ala missense NM_001322014.2:c.1424T>C NP_001308943.1:p.Val475Ala missense NM_001322015.2:c.1115T>C NP_001308944.1:p.Val372Ala missense NM_001406866.1:c.1610T>C NP_001393795.1:p.Val537Ala missense NM_001406868.1:c.1448T>C NP_001393797.1:p.Val483Ala missense NM_001406869.1:c.1316T>C NP_001393798.1:p.Val439Ala missense NM_001406870.1:c.1268T>C NP_001393799.1:p.Val423Ala missense NM_001406871.1:c.1424T>C NP_001393800.1:p.Val475Ala missense NM_001406872.1:c.1424T>C NP_001393801.1:p.Val475Ala missense NM_001406873.1:c.1226T>C NP_001393802.1:p.Val409Ala missense NM_001406874.1:c.1256T>C NP_001393803.1:p.Val419Ala missense NM_001406875.1:c.1115T>C NP_001393804.1:p.Val372Ala missense NM_001406876.1:c.1106T>C NP_001393805.1:p.Val369Ala missense NM_001406877.1:c.1115T>C NP_001393806.1:p.Val372Ala missense NM_001406878.1:c.1115T>C NP_001393807.1:p.Val372Ala missense NM_001406879.1:c.1115T>C NP_001393808.1:p.Val372Ala missense NM_001406880.1:c.1115T>C NP_001393809.1:p.Val372Ala missense NM_001406881.1:c.1115T>C NP_001393810.1:p.Val372Ala missense NM_001406882.1:c.1115T>C NP_001393811.1:p.Val372Ala missense NM_001406883.1:c.1106T>C NP_001393812.1:p.Val369Ala missense NM_001406884.1:c.1100T>C NP_001393813.1:p.Val367Ala missense NM_001406885.1:c.1088T>C NP_001393814.1:p.Val363Ala missense NM_001406886.1:c.1058T>C NP_001393815.1:p.Val353Ala missense NM_001406887.1:c.1019T>C NP_001393816.1:p.Val340Ala missense NM_001406888.1:c.1019T>C NP_001393817.1:p.Val340Ala missense NM_001406889.1:c.1019T>C NP_001393818.1:p.Val340Ala missense NM_001406890.1:c.1019T>C NP_001393819.1:p.Val340Ala missense NM_001406891.1:c.1019T>C NP_001393820.1:p.Val340Ala missense NM_001406892.1:c.1019T>C NP_001393821.1:p.Val340Ala missense NM_001406893.1:c.1019T>C NP_001393822.1:p.Val340Ala missense NM_001406894.1:c.1019T>C NP_001393823.1:p.Val340Ala missense NM_001406895.1:c.1019T>C NP_001393824.1:p.Val340Ala missense NM_001406896.1:c.1019T>C NP_001393825.1:p.Val340Ala missense NM_001406897.1:c.1019T>C NP_001393826.1:p.Val340Ala missense NM_001406898.1:c.1019T>C NP_001393827.1:p.Val340Ala missense NM_001406899.1:c.1019T>C NP_001393828.1:p.Val340Ala missense NM_001406900.1:c.959T>C NP_001393829.1:p.Val320Ala missense NM_001406901.1:c.950T>C NP_001393830.1:p.Val317Ala missense NM_001406902.1:c.950T>C NP_001393831.1:p.Val317Ala missense NM_001406903.1:c.1106T>C NP_001393832.1:p.Val369Ala missense NM_001406904.1:c.911T>C NP_001393833.1:p.Val304Ala missense NM_001406905.1:c.911T>C NP_001393834.1:p.Val304Ala missense NM_001406906.1:c.863T>C NP_001393835.1:p.Val288Ala missense NM_001406907.1:c.863T>C NP_001393836.1:p.Val288Ala missense NM_001406908.1:c.1019T>C NP_001393837.1:p.Val340Ala missense NM_001406909.1:c.851T>C NP_001393838.1:p.Val284Ala missense NM_001406910.1:c.1019T>C NP_001393839.1:p.Val340Ala missense NM_001406911.1:c.653T>C NP_001393840.1:p.Val218Ala missense NR_003085.2:n.1506T>C NR_136154.1:n.1511T>C non-coding transcript variant NC_000007.14:g.5987341A>G NC_000007.13:g.6026972A>G NG_008466.1:g.26766T>C LRG_161:g.26766T>C LRG_161t1:c.1424T>C LRG_161p1:p.Val475Ala - Protein change
- V353A, V363A, V367A, V372A, V439A, V164A, V218A, V423A, V475A, V284A, V304A, V317A, V320A, V369A, V409A, V288A, V340A, V419A, V483A, V537A
- Other names
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- Canonical SPDI
- NC_000007.14:5987340:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| PMS2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5241 | 5343 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Likely benign (1) |
criteria provided, single submitter
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Mar 30, 2022 | RCV002391902.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Likely benign
(Mar 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002698662.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.