NM_022455.5(NSD1):c.3031del (p.Ser1011fs) AND Sotos syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 26, 2021
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:: RCV003232487.9

Allele description [Variation Report for NM_022455.5(NSD1):c.3031del (p.Ser1011fs)]

NM_022455.5(NSD1):c.3031del (p.Ser1011fs)

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.3031del (p.Ser1011fs)

HGVS:

NC_000005.10:g.177211430del
NG_009821.1:g.83352del
NM_001365684.2:c.2158delA
NM_001409301.1:c.3031delA
NM_001409302.1:c.3031delA
NM_001409303.1:c.3031delA
NM_001409304.1:c.2611delA
NM_001409305.1:c.2278delA
NM_001409306.1:c.2158delA
NM_001409307.1:c.2158delA
NM_001409308.1:c.2158delA
NM_001409309.1:c.2158delA
NM_022455.5:c.3031delMANE SELECT
NM_172349.5:c.2158delA
NP_001352613.1:p.Ser742fs
NP_001352613.2:p.Ser720Valfs
NP_001396230.1:p.Ser1011Valfs
NP_001396231.1:p.Ser1011Valfs
NP_001396232.1:p.Ser1011Valfs
NP_001396233.1:p.Ser871Valfs
NP_001396234.1:p.Ser760Valfs
NP_001396235.1:p.Ser720Valfs
NP_001396236.1:p.Ser720Valfs
NP_001396237.1:p.Ser720Valfs
NP_001396238.1:p.Ser720Valfs
NP_071900.2:p.Ser1011Valfs
NP_071900.2:p.Ser1011fs
NP_758859.1:p.Ser742fs
NP_758859.2:p.Ser720Valfs
LRG_512t1:c.3031del
LRG_512:g.83352del
LRG_512p1:p.Ser1011Valfs
NC_000005.9:g.176638428del
NC_000005.9:g.176638431del
NM_001365684.1:c.2224del
NM_022455.4:c.3031delA
NM_172349.3:c.2224del

Protein change:

S1011fs

Links:

dbSNP: rs2149846959

NCBI 1000 Genomes Browser:

rs2149846959

Molecular consequence:

NM_001365684.2:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409301.1:c.3031delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409302.1:c.3031delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409303.1:c.3031delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409304.1:c.2611delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409305.1:c.2278delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409306.1:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409307.1:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409308.1:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001409309.1:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022455.5:c.3031del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172349.5:c.2158delA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Sotos syndrome (SOTOS)
Synonyms:: Sotos' syndrome; Cerebral gigantism; Distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development; 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
SCV002229760	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 26, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12464997, 14571271, 15942875, 16247291, 28475857, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002229760

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 26, 2021)

germline

clinical testing

PubMed (6)
[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

NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.

Douglas J, Hanks S, Temple IK, Davies S, Murray A, Upadhyaya M, Tomkins S, Hughes HE, Cole TR, Rahman N.

Am J Hum Genet. 2003 Jan;72(1):132-43. Epub 2002 Dec 2.

PubMed [citation]

PMID:: 12464997
PMCID:: PMC378618

Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.

Türkmen S, Gillessen-Kaesbach G, Meinecke P, Albrecht B, Neumann LM, Hesse V, Palanduz S, Balg S, Majewski F, Fuchs S, Zschieschang P, Greiwe M, Mennicke K, Kreuz FR, Dehmel HJ, Rodeck B, Kunze J, Tinschert S, Mundlos S, Horn D.

Eur J Hum Genet. 2003 Nov;11(11):858-65.

PubMed [citation]

PMID:: 14571271

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002229760.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Ser1011Valfs*29) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with intellectual disability and overgrowth (PMID: 28475857). 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: Nov 10, 2024

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