NM_001372044.2(SHANK3):c.3286del (p.Glu1096fs) AND Phelan-McDermid syndrome

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003985982.1

Allele description [Variation Report for NM_001372044.2(SHANK3):c.3286del (p.Glu1096fs)]

NM_001372044.2(SHANK3):c.3286del (p.Glu1096fs)

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.3286del (p.Glu1096fs)

HGVS:

NC_000022.11:g.50720894del
NG_070230.1:g.56678del
NM_001372044.2:c.3286delMANE SELECT
NM_033517.1:c.3061delG
NP_001358973.1:p.Glu1096fs
NP_277052.1:p.Glu1021Argfs
NC_000022.10:g.51159322del

Protein change:

E1096fs

Molecular consequence:

NM_001372044.2:c.3286del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033517.1:c.3061delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Phelan-McDermid syndrome
Synonyms:: TELOMERIC 22q13 MONOSOMY SYNDROME; 22q13.3 deletion syndrome; Chromosome 22q13.3 deletion syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011652; MedGen: C1853490; Orphanet: 48652; OMIM: 606232

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004801802	Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV004801802

Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, SCV004801802.1

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

Description

A previously undescribed nucleotide variant creates a frameshift p.Ala1096ProfsTer44 in the SHANK3 gene. The variant was observed in heterozygous state in an individual affected with autistic spectrum disorder, cerebral palsy, and dysmorpic features. Loss-of-function variants are reported in patients with Phelan-McDermid syndrome, 606232. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.

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

Last Updated: Mar 30, 2024

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