The p.N683H variant (also known as c.2047A>C), located in coding exon 12 of the PMS2 gene, results from an A to C substitution at nucleotide position 2047. The asparagine at codon 683 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.2047A>C (p.Asn683His)
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)
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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.
Uncertain significance
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.2047A>C (p.Asn683His)
Variation ID: 2451605 Accession: VCV002451605.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5982951 (GRCh38) [ NCBI UCSC ] 7: 6022582 (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 Apr 15, 2023 May 1, 2024 Jan 15, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.2047A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Asn683His missense NM_001018040.1:c.1642A>C NP_001018050.1:p.Asn548His missense NM_001322003.2:c.1642A>C NP_001308932.1:p.Asn548His missense NM_001322004.2:c.1642A>C NP_001308933.1:p.Asn548His missense NM_001322005.2:c.1642A>C NP_001308934.1:p.Asn548His missense NM_001322006.2:c.1891A>C NP_001308935.1:p.Asn631His missense NM_001322007.2:c.1729A>C NP_001308936.1:p.Asn577His missense NM_001322008.2:c.1729A>C NP_001308937.1:p.Asn577His missense NM_001322009.2:c.1642A>C NP_001308938.1:p.Asn548His missense NM_001322010.2:c.1486A>C NP_001308939.1:p.Asn496His missense NM_001322011.2:c.1114A>C NP_001308940.1:p.Asn372His missense NM_001322012.2:c.1114A>C NP_001308941.1:p.Asn372His missense NM_001322013.2:c.1474A>C NP_001308942.1:p.Asn492His missense NM_001322014.2:c.2047A>C NP_001308943.1:p.Asn683His missense NM_001322015.2:c.1738A>C NP_001308944.1:p.Asn580His missense NM_001406866.1:c.2233A>C NP_001393795.1:p.Asn745His missense NM_001406868.1:c.2071A>C NP_001393797.1:p.Asn691His missense NM_001406869.1:c.1939A>C NP_001393798.1:p.Asn647His missense NM_001406870.1:c.1891A>C NP_001393799.1:p.Asn631His missense NM_001406871.1:c.2047A>C NP_001393800.1:p.Asn683His missense NM_001406872.1:c.2006+3808A>C intron variant NM_001406873.1:c.1849A>C NP_001393802.1:p.Asn617His missense NM_001406874.1:c.1879A>C NP_001393803.1:p.Asn627His missense NM_001406875.1:c.1738A>C NP_001393804.1:p.Asn580His missense NM_001406876.1:c.1729A>C NP_001393805.1:p.Asn577His missense NM_001406877.1:c.1738A>C NP_001393806.1:p.Asn580His missense NM_001406878.1:c.1738A>C NP_001393807.1:p.Asn580His missense NM_001406879.1:c.1738A>C NP_001393808.1:p.Asn580His missense NM_001406880.1:c.1738A>C NP_001393809.1:p.Asn580His missense NM_001406881.1:c.1738A>C NP_001393810.1:p.Asn580His missense NM_001406882.1:c.1738A>C NP_001393811.1:p.Asn580His missense NM_001406883.1:c.1729A>C NP_001393812.1:p.Asn577His missense NM_001406884.1:c.1723A>C NP_001393813.1:p.Asn575His missense NM_001406885.1:c.1711A>C NP_001393814.1:p.Asn571His missense NM_001406886.1:c.1681A>C NP_001393815.1:p.Asn561His missense NM_001406887.1:c.1642A>C NP_001393816.1:p.Asn548His missense NM_001406888.1:c.1642A>C NP_001393817.1:p.Asn548His missense NM_001406889.1:c.1642A>C NP_001393818.1:p.Asn548His missense NM_001406890.1:c.1642A>C NP_001393819.1:p.Asn548His missense NM_001406891.1:c.1642A>C NP_001393820.1:p.Asn548His missense NM_001406892.1:c.1642A>C NP_001393821.1:p.Asn548His missense NM_001406893.1:c.1642A>C NP_001393822.1:p.Asn548His missense NM_001406894.1:c.1642A>C NP_001393823.1:p.Asn548His missense NM_001406895.1:c.1642A>C NP_001393824.1:p.Asn548His missense NM_001406896.1:c.1642A>C NP_001393825.1:p.Asn548His missense NM_001406897.1:c.1642A>C NP_001393826.1:p.Asn548His missense NM_001406898.1:c.1642A>C NP_001393827.1:p.Asn548His missense NM_001406899.1:c.1642A>C NP_001393828.1:p.Asn548His missense NM_001406900.1:c.1582A>C NP_001393829.1:p.Asn528His missense NM_001406901.1:c.1573A>C NP_001393830.1:p.Asn525His missense NM_001406902.1:c.1573A>C NP_001393831.1:p.Asn525His missense NM_001406903.1:c.1688+3808A>C intron variant NM_001406904.1:c.1534A>C NP_001393833.1:p.Asn512His missense NM_001406905.1:c.1534A>C NP_001393834.1:p.Asn512His missense NM_001406906.1:c.1486A>C NP_001393835.1:p.Asn496His missense NM_001406907.1:c.1486A>C NP_001393836.1:p.Asn496His missense NM_001406908.1:c.1601+3808A>C intron variant NM_001406909.1:c.1474A>C NP_001393838.1:p.Asn492His missense NM_001406910.1:c.1601+3808A>C intron variant NM_001406911.1:c.1276A>C NP_001393840.1:p.Asn426His missense NM_001406912.1:c.844A>C NP_001393841.1:p.Asn282His missense NR_003085.2:n.2129A>C NR_136154.1:n.2134A>C non-coding transcript variant NC_000007.14:g.5982951T>G NC_000007.13:g.6022582T>G NG_008466.1:g.31156A>C LRG_161:g.31156A>C LRG_161t1:c.2047A>C LRG_161p1:p.Asn683His - Protein change
- N372H, N426H, N525H, N548H, N561H, N282H, N631H, N647H, N691H, N745H, N496H, N528H, N577H, N617H, N627H, N492H, N512H, N571H, N575H, N580H, N683H
- Other names
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- Canonical SPDI
- NC_000007.14:5982950:T: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. |
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| 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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Jan 15, 2023 | RCV003187301.2 |
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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Uncertain significance
(Jan 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003853906.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The p.N683H variant (also known as c.2047A>C), located in coding exon 12 of the PMS2 gene, results from an A to C substitution at nucleotide … (more)
The p.N683H variant (also known as c.2047A>C), located in coding exon 12 of the PMS2 gene, results from an A to C substitution at nucleotide position 2047. The asparagine at codon 683 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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:
The p.N683H variant (also known as c.2047A>C), located in coding exon 12 of the PMS2 gene, results from an A to C substitution at nucleotide position 2047. The asparagine at codon 683 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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.