NM_005337.5(NCKAP1L):c.1555G>C (p.Val519Leu) AND Immunodeficiency 72 with autoinflammation

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 13, 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:: RCV001254325.3

Allele description [Variation Report for NM_005337.5(NCKAP1L):c.1555G>C (p.Val519Leu)]

NM_005337.5(NCKAP1L):c.1555G>C (p.Val519Leu)

Gene:

NCKAP1L:NCK associated protein 1 like [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.2

Genomic location:

Preferred name:

NM_005337.5(NCKAP1L):c.1555G>C (p.Val519Leu)

HGVS:

NC_000012.12:g.54519262G>C
NM_001184976.2:c.1405G>C
NM_005337.5:c.1555G>CMANE SELECT
NP_001171905.1:p.Val469Leu
NP_005328.2:p.Val519Leu
NC_000012.11:g.54913046G>C
NM_005337.4:c.1555G>C

Protein change:

V469L; VAL519LEU

Links:

OMIM: 141180.0002; dbSNP: rs1956961224

NCBI 1000 Genomes Browser:

rs1956961224

Molecular consequence:

NM_001184976.2:c.1405G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005337.5:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Immunodeficiency 72 with autoinflammation
Synonyms:: IMMUNODEFICIENCY 72 WITH AUTOINFLAMMATION AND LYMPHOPROLIFERATION
Identifiers:: MONDO: MONDO:0033551; MedGen: C5436540; OMIM: 618982

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001430307	OMIM	no assertion criteria provided	Pathogenic (Mar 15, 2023)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001571385	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 13, 2021)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 32647003, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001430307

OMIM

no assertion criteria provided

Pathogenic
(Mar 15, 2023)

germline

literature only

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

SCV001571385

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 13, 2021)

unknown

curation

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.

Cook SA, Comrie WA, Poli MC, Similuk M, Oler AJ, Faruqi AJ, Kuhns DB, Yang S, Vargas-Hernández A, Carisey AF, Fournier B, Anderson DE, Price S, Smelkinson M, Abou Chahla W, Forbes LR, Mace EM, Cao TN, Coban-Akdemir ZH, Jhangiani SN, Muzny DM, Gibbs RA, et al.

Science. 2020 Jul 10;369(6500):202-207. doi: 10.1126/science.aay5663.

PubMed [citation]

PMID:: 32647003
PMCID:: PMC8383235

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 OMIM, SCV001430307.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the c.1555G-C transversion (c.1555G-C, NM_005337.4) in the NCKAP1L gene, resulting in a val519-to-leu (V519L) substitution, that was found in compound heterozygous state in 2 sibs with immunodeficiency-72 with autoinflammation and lymphoproliferation (IMD72; 618982) by Cook et al. (2020), see 141180.0001.

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

From SIB Swiss Institute of Bioinformatics, SCV001571385.1

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

Description

This variant is interpreted as likely pathogenic for Immunodeficiency 72 with autoinflammation, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Well-established functional studies show a deleterious effect (PS3); For recessive disorders, detected in trans with a likely pathogenic/pathogenic variant (PM3).

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

Last Updated: Mar 18, 2023

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