NM_013314.4(BLNK):c.1098T>G (p.Asp366Glu) AND Agammaglobulinemia 4, autosomal recessive

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

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001369290.8

Allele description

NM_013314.4(BLNK):c.1098T>G (p.Asp366Glu)

Genes:

BLNK:B cell linker [Gene - OMIM - HGNC]
ZNF518A:zinc finger protein 518A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.1

Genomic location:

Preferred name:

NM_013314.4(BLNK):c.1098T>G (p.Asp366Glu)

HGVS:

NC_000010.11:g.96197061A>C
NG_007575.1:g.84510T>G
NG_033267.2:g.72842A>C
NM_001114094.2:c.1029T>G
NM_001258440.2:c.1095+3014T>G
NM_001258441.2:c.1026+3014T>G
NM_001258442.2:c.780+3014T>G
NM_013314.3:c.1098T>G
NM_013314.4:c.1098T>GMANE SELECT
NP_001107566.1:p.Asp343Glu
NP_037446.1:p.Asp366Glu
LRG_21t1:c.1098T>G
LRG_21:g.84510T>G
NC_000010.10:g.97956817A>C
NR_047680.2:n.1093T>G
NR_047681.2:n.1041T>G
NR_047682.2:n.1036T>G

Protein change:

D343E

Links:

dbSNP: rs782205113

NCBI 1000 Genomes Browser:

rs782205113

Molecular consequence:

NM_001258440.2:c.1095+3014T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001258441.2:c.1026+3014T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001258442.2:c.780+3014T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001114094.2:c.1029T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_013314.4:c.1098T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_047680.2:n.1093T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047681.2:n.1041T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047682.2:n.1036T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Agammaglobulinemia 4, autosomal recessive (AGM4)
Synonyms:: AGAMMAGLOBULINEMIA, AUTOSOMAL RECESSIVE, DUE TO BLNK DEFECT
Identifiers:: MONDO: MONDO:0013289; MedGen: C3150752; OMIM: 613502

Recent activity

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RefSeq RNA Links for Gene (Select 118253407) (38)
Nucleotide
Xanthomonas oryzae pv. oryzae strain ScYc-b chromosome, complete genome
Xanthomonas oryzae pv. oryzae strain ScYc-b chromosome, complete genome
gi|1450026732|ref|NZ_CP031469.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001565724	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003831474	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 23, 2021)	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

SCV001565724

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2022)

germline

clinical testing

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

SCV003831474

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 23, 2021)

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

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 Invitae, SCV001565724.3

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 366 of the BLNK protein (p.Asp366Glu). This variant is present in population databases (rs782205113, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with BLNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1059928). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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

From Revvity Omics, Revvity, SCV003831474.2

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

#	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: Mar 16, 2024

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