NM_001082486.2(ACD):c.1370_1371delinsTT (p.Pro457Leu) AND Dyskeratosis congenita, autosomal dominant 6

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 23, 2020
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:: RCV001370989.6

Allele description [Variation Report for NM_001082486.2(ACD):c.1370_1371delinsTT (p.Pro457Leu)]

NM_001082486.2(ACD):c.1370_1371delinsTT (p.Pro457Leu)

Gene:

ACD:ACD shelterin complex subunit and telomerase recruitment factor [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_001082486.2(ACD):c.1370_1371delinsTT (p.Pro457Leu)

HGVS:

NC_000016.10:g.67657612_67657613delinsAA
NG_042874.1:g.8203_8204delinsTT
NG_054728.1:g.17694_17695delinsAA
NM_001082486.2:c.1370_1371delinsTTMANE SELECT
NM_022914.3:c.1361_1362delinsTT
NP_001075955.2:p.Pro457Leu
NP_075065.3:p.Pro454Leu
LRG_1237t1:c.1370_1371delinsTT
LRG_1237:g.8203_8204delinsTT
LRG_1237p1:p.Pro457Leu
NC_000016.9:g.67691515_67691516delinsAA

Protein change:

P454L

Links:

dbSNP: rs2142965523

NCBI 1000 Genomes Browser:

rs2142965523

Molecular consequence:

NM_001082486.2:c.1370_1371delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_022914.3:c.1361_1362delinsTT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dyskeratosis congenita, autosomal dominant 6 (DKCA6)
Identifiers:: MONDO: MONDO:0014690; MedGen: C4225284; Orphanet: 3322; OMIM: 616553

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001567539	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001567539

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 23, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001567539.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals with ACD-related conditions. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change replaces proline with leucine at codon 543 of the ACD protein (p.Pro543Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine