NM_145207.3(AFG2A):c.661C>T (p.Gln221Ter) AND Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 2017
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:: RCV000652803.2

Allele description [Variation Report for NM_145207.3(AFG2A):c.661C>T (p.Gln221Ter)]

NM_145207.3(AFG2A):c.661C>T (p.Gln221Ter)

Gene:

AFG2A:AFG2 AAA ATPase homolog A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q28.1

Genomic location:

Preferred name:

NM_145207.3(AFG2A):c.661C>T (p.Gln221Ter)

HGVS:

NC_000004.12:g.122934252C>T
NG_051570.1:g.16183C>T
NM_001317799.2:c.658C>T
NM_001345856.2:c.658C>T
NM_145207.3:c.661C>TMANE SELECT
NP_001304728.1:p.Gln220Ter
NP_001332785.1:p.Gln220Ter
NP_660208.2:p.Gln221Ter
NC_000004.11:g.123855407C>T
NM_145207.2:c.661C>T

Protein change:

Q220*

Links:

dbSNP: rs1553955672

NCBI 1000 Genomes Browser:

rs1553955672

Molecular consequence:

NM_001317799.2:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001345856.2:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145207.3:c.661C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (NEDHSB)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH HEARING LOSS, SEIZURES, AND BRAIN ABNORMALITIES
Identifiers:: MONDO: MONDO:0014698; MedGen: C4225276; Orphanet: 457351; OMIM: 616577

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000774675	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26299366, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000774675

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2017)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in SPATA5 Are Associated with Microcephaly, Intellectual Disability, Seizures, and Hearing Loss.

Tanaka AJ, Cho MT, Millan F, Juusola J, Retterer K, Joshi C, Niyazov D, Garnica A, Gratz E, Deardorff M, Wilkins A, Ortiz-Gonzalez X, Mathews K, Panzer K, Brilstra E, van Gassen KL, Volker-Touw CM, van Binsbergen E, Sobreira N, Hamosh A, McKnight D, Monaghan KG, et al.

Am J Hum Genet. 2015 Sep 3;97(3):457-64. doi: 10.1016/j.ajhg.2015.07.014. Epub 2015 Aug 20.

PubMed [citation]

PMID:: 26299366
PMCID:: PMC4564988

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000774675.2

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

Description

This sequence change creates a premature translational stop signal (p.Gln221*) in the SPATA5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPATA5-related disease. Loss-of-function variants in SPATA5 are known to be pathogenic (PMID: 26299366). For these reasons, this variant has been classified as Pathogenic.

#	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: Aug 5, 2023

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