NM_000077.5(CDKN2A):c.284T>A (p.Val95Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 9, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002435350.2

Allele description [Variation Report for NM_000077.5(CDKN2A):c.284T>A (p.Val95Glu)]

NM_000077.5(CDKN2A):c.284T>A (p.Val95Glu)

Gene:

CDKN2A:cyclin dependent kinase inhibitor 2A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p21.3

Genomic location:

Preferred name:

NM_000077.5(CDKN2A):c.284T>A (p.Val95Glu)

HGVS:

NC_000009.12:g.21971075A>T
NG_007485.1:g.28417T>A
NM_000077.5:c.284T>AMANE SELECT
NM_001195132.2:c.284T>A
NM_001363763.2:c.131T>A
NM_058195.4:c.327T>A
NM_058197.5:c.*207T>A
NP_000068.1:p.Val95Glu
NP_000068.1:p.Val95Glu
NP_001182061.1:p.Val95Glu
NP_001350692.1:p.Val44Glu
NP_478102.2:p.Gly109=
NP_478102.2:p.Gly109=
LRG_11t1:c.284T>A
LRG_11t2:c.327T>A
LRG_11:g.28417T>A
LRG_11p1:p.Val95Glu
LRG_11p2:p.Gly109=
NC_000009.11:g.21971074A>T
NM_000077.4:c.284T>A
NM_058195.3:c.327T>A

Protein change:

V44E

Molecular consequence:

NM_058197.5:c.*207T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000077.5:c.284T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.284T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363763.2:c.131T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058195.4:c.327T>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002751807	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 9, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12454511, 21462282 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002751807

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 9, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CDKN2A germline mutations in familial pancreatic cancer.

Bartsch DK, Sina-Frey M, Lang S, Wild A, Gerdes B, Barth P, Kress R, Grützmann R, Colombo-Benkmann M, Ziegler A, Hahn SA, Rothmund M, Rieder H.

Ann Surg. 2002 Dec;236(6):730-7.

PubMed [citation]

PMID:: 12454511
PMCID:: PMC1422639

Classifying variants of CDKN2A using computational and laboratory studies.

Miller PJ, Duraisamy S, Newell JA, Chan PA, Tie MM, Rogers AE, Ankuda CK, von Walstrom GM, Bond JP, Greenblatt MS.

Hum Mutat. 2011 Aug;32(8):900-11. doi: 10.1002/humu.21504.

PubMed [citation]

PMID:: 21462282

Details of each submission

From Ambry Genetics, SCV002751807.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.V95E variant (also known as c.284T>A), located in coding exon 2 of the CDKN2A gene, results from a T to A substitution at nucleotide position 284. The valine at codon 95 is replaced by glutamic acid, an amino acid with dissimilar properties. In a computational study utilizing a Bayesian method to combine multiple data types, this alteration was classified as having unknown functional consequence with cumulative odds of pathogenicity of 0.018 (Miller PJ et al. Hum Mutat, 2011 Aug;32:900-11). This alteration has been identified in the germline of a 58-year-old patient with personal and family history of pancreatic cancer, but p.V95E was also detected in two control individuals from this study, so authors concluded that this alteration was not associated with disease (Bartsch DK et al. Ann Surg, 2002 Dec;236:730-7). This amino acid position is not well conserved in available vertebrate species. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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