NM_013436.5(NCKAP1):c.1861C>T (p.Gln621Ter) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 2023
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:: RCV003412546.1

Allele description

NM_013436.5(NCKAP1):c.1861C>T (p.Gln621Ter)

Gene:

NCKAP1:NCK associated protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.1

Genomic location:

Preferred name:

NM_013436.5(NCKAP1):c.1861C>T (p.Gln621Ter)

HGVS:

NC_000002.12:g.182962179G>A
NM_013436.5:c.1861C>TMANE SELECT
NM_205842.3:c.1879C>T
NP_038464.1:p.Gln621Ter
NP_995314.1:p.Gln627Ter
NC_000002.11:g.183826907G>A

Protein change:

Q621*

Molecular consequence:

NM_013436.5:c.1861C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_205842.3:c.1879C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Autistic behavior
Identifiers:: MedGen: C0856975; Human Phenotype Ontology: HP:0000729

Name:: Neurodevelopmental abnormality
Identifiers:: MedGen: C4022737; Human Phenotype Ontology: HP:0012759

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004101724	Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 4, 2023)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33157009, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004101724

Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 4, 2023)

de novo

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.

Guo H, Zhang Q, Dai R, Yu B, Hoekzema K, Tan J, Tan S, Jia X, Chung WK, Hernan R, Alkuraya FS, Alsulaiman A, Al-Muhaizea MA, Lesca G, Pons L, Labalme A, Laux L, Bryant E, Brown NJ, Savva E, Ayres S, Eratne D, et al.

Am J Hum Genet. 2020 Nov 5;107(5):963-976. doi: 10.1016/j.ajhg.2020.10.002.

PubMed [citation]

PMID:: 33157009
PMCID:: PMC7674997

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen, SCV004101724.1

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

Description

The variant has not been detected in the general population (gnomAD). It has not yet been described in the literature or in the ClinVar and dbSNP151 databases. In the case of stop or nonsense variants in a gene matching the phenotype (and matching inheritance), in which "loss of function" changes represent a known pathomechanism, pathogenetic relevance can be assumed with high probability. Based on current knowledge, the variant is to be classified as "pathogenic" (ACMG criteria).

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

Last Updated: Nov 25, 2023

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