NM_022455.5(NSD1):c.4776del (p.Cys1593fs) AND Sotos syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 29, 2022
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:: RCV003232620.9

Allele description [Variation Report for NM_022455.5(NSD1):c.4776del (p.Cys1593fs)]

NM_022455.5(NSD1):c.4776del (p.Cys1593fs)

Gene:

NSD1:nuclear receptor binding SET domain protein 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_022455.5(NSD1):c.4776del (p.Cys1593fs)

HGVS:

NC_000005.10:g.177256961del
NG_009821.1:g.128883del
NM_001365684.2:c.3903delC
NM_001409301.1:c.4776delC
NM_001409302.1:c.4776delC
NM_001409303.1:c.4776delC
NM_001409304.1:c.4356delC
NM_001409305.1:c.4023delC
NM_001409306.1:c.4014delC
NM_001409307.1:c.4014delC
NM_001409308.1:c.3903delC
NM_001409309.1:c.3903delC
NM_022455.5:c.4776delMANE SELECT
NM_172349.5:c.3903delC
NP_001352613.1:p.Cys1324fs
NP_001352613.2:p.Cys1302Valfs
NP_001396230.1:p.Cys1593Valfs
NP_001396231.1:p.Cys1593Valfs
NP_001396232.1:p.Cys1593Valfs
NP_001396233.1:p.Cys1453Valfs
NP_001396234.1:p.Cys1342Valfs
NP_001396235.1:p.Cys1339Valfs
NP_001396236.1:p.Cys1339Valfs
NP_001396237.1:p.Cys1302Valfs
NP_001396238.1:p.Cys1302Valfs
NP_071900.2:p.Cys1593Valfs
NP_071900.2:p.Cys1593fs
NP_758859.1:p.Cys1324fs
NP_758859.2:p.Cys1302Valfs
LRG_512t1:c.4776del
LRG_512:g.128883del
LRG_512p1:p.Cys1593Valfs
NC_000005.9:g.176683962del
NM_001365684.1:c.3969del
NM_022455.4:c.4776delC
NM_172349.3:c.3969del

Protein change:

C1324fs

Links:

dbSNP: rs2480663838

NCBI 1000 Genomes Browser:

rs2480663838

Molecular consequence:

NM_001365684.2:c.3903delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409301.1:c.4776delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409302.1:c.4776delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409303.1:c.4776delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409304.1:c.4356delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409305.1:c.4023delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409306.1:c.4014delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409307.1:c.4014delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409308.1:c.3903delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409309.1:c.3903delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022455.5:c.4776del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172349.5:c.3903delC - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Sotos syndrome (SOTOS)
Synonyms:: Sotos' syndrome; Distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development; CHROMOSOME 5q35 DELETION SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019349; MedGen: C0175695; Orphanet: 821; OMIM: 117550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002756470	Institute of Human Genetics, University of Goettingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 29, 2022)	unknown	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

SCV002756470

Institute of Human Genetics, University of Goettingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 29, 2022)

unknown

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	unknown	yes	1	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 Institute of Human Genetics, University of Goettingen, SCV002756470.2

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

Description

The variant c.4776del (p.(Cys1593Valfs*49)) in exon 13 of the NSD1 gene is not found in the gnomAD database and it creates a frame shift starting at codon Cys1593. The new reading frame ends in a STOP codon at position 49. ACMG criteria used for classification: PVS1, PM2.

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

Last Updated: May 16, 2025

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