NM_001372044.2(SHANK3):c.3989_4001del (p.Arg1330fs) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 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:: RCV001267260.8

Allele description [Variation Report for NM_001372044.2(SHANK3):c.3989_4001del (p.Arg1330fs)]

NM_001372044.2(SHANK3):c.3989_4001del (p.Arg1330fs)

Gene:

SHANK3:SH3 and multiple ankyrin repeat domains 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_001372044.2(SHANK3):c.3989_4001del (p.Arg1330fs)

Other names:

NM_001080420.1:c.3812_3824del

HGVS:

NC_000022.11:g.50721597_50721609del
NG_070230.1:g.57381_57393del
NM_001372044.2:c.3989_4001delMANE SELECT
NM_033517.1:c.3764_3776del
NP_001358973.1:p.Arg1330fs
NP_277052.1:p.Arg1255Leufs
NP_277052.1:p.Arg1255fs
NC_000022.10:g.51160025_51160037del
NM_033517.1:c.3764_3776del13
NM_033517.1:c.3764_3776delGGGCCCAGCCCCC

Protein change:

R1255fs

Links:

dbSNP: rs886041238

NCBI 1000 Genomes Browser:

rs886041238

Molecular consequence:

NM_001372044.2:c.3989_4001del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033517.1:c.3764_3776del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001445441	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 27, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25188300, 28135719, 29719671 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001445441

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 27, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.

Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, Giuliano F, Stordeur C, Depienne C, Mouzat K, Pinto D, Howe J, Lemière N, Durand CM, Guibert J, Ey E, Toro R, Peyre H, Mathieu A, Amsellem F, Rastam M, Gillberg IC, et al.

PLoS Genet. 2014 Sep;10(9):e1004580. doi: 10.1371/journal.pgen.1004580.

PubMed [citation]

PMID:: 25188300
PMCID:: PMC4154644

Prevalence and architecture of de novo mutations in developmental disorders.

Deciphering Developmental Disorders Study..

Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.

PubMed [citation]

PMID:: 28135719
PMCID:: PMC6016744

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV001445441.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The alteration results in a premature stop codon: _x000D_ _x000D_ The c.3764_3776del13 (p.R1255Lfs*25) alteration, located in coding exon 21 of the SHANK3 gene, results from a deletion of 13 nucleotides from position 3764 to 3776, causing a translational frameshift with a predicted alternate stop codon after 25 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. The alteration has been observed in affected individuals: _x000D_ _x000D_ The alteration has been reported as a de novo occurrence in individuals with a diagnosis of, or features consistent with, Phelan-McDermid Syndrome (De Rubeis, 2018; Leblond, 2014), as well as in an individual with an unspecified developmental disorder (Deciphering Developmental Disorders Study, 2017). Based on the available evidence, this alteration is 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: Oct 20, 2024

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