NM_001330078.2(NRXN1):c.3731A>G (p.Asn1244Ser) AND Pitt-Hopkins-like syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 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:: RCV001937829.6

Allele description [Variation Report for NM_001330078.2(NRXN1):c.3731A>G (p.Asn1244Ser)]

NM_001330078.2(NRXN1):c.3731A>G (p.Asn1244Ser)

Gene:

NRXN1:neurexin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_001330078.2(NRXN1):c.3731A>G (p.Asn1244Ser)

HGVS:

NC_000002.12:g.50055032T>C
NG_011878.1:g.982505A>G
NM_001135659.3:c.3851A>G
NM_001330077.2:c.3707A>G
NM_001330078.2:c.3731A>GMANE SELECT
NM_001330082.2:c.3707A>G
NM_001330083.2:c.3653-1442A>G
NM_001330084.2:c.3665A>G
NM_001330085.2:c.3704A>G
NM_001330086.2:c.3731A>G
NM_001330087.2:c.3608-1442A>G
NM_001330088.2:c.3638-1442A>G
NM_001330091.2:c.626A>G
NM_001330092.2:c.626A>G
NM_001330093.2:c.3728A>G
NM_001330094.2:c.3719A>G
NM_001330095.2:c.3668-1442A>G
NM_001330096.2:c.3608-1442A>G
NM_001330097.2:c.614-1442A>G
NM_004801.6:c.3719-1442A>G
NM_138735.5:c.614-1442A>G
NP_001129131.1:p.Asn1284Ser
NP_001317006.1:p.Asn1236Ser
NP_001317007.1:p.Asn1244Ser
NP_001317011.1:p.Asn1236Ser
NP_001317013.1:p.Asn1222Ser
NP_001317014.1:p.Asn1235Ser
NP_001317015.1:p.Asn1244Ser
NP_001317020.1:p.Asn209Ser
NP_001317021.1:p.Asn209Ser
NP_001317022.1:p.Asn1243Ser
NP_001317023.1:p.Asn1240Ser
NC_000002.11:g.50282170T>C

Protein change:

N1222S

Links:

dbSNP: rs772457165

NCBI 1000 Genomes Browser:

rs772457165

Molecular consequence:

NM_001330083.2:c.3653-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330087.2:c.3608-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330088.2:c.3638-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330095.2:c.3668-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330096.2:c.3608-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330097.2:c.614-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004801.6:c.3719-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_138735.5:c.614-1442A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001135659.3:c.3851A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330077.2:c.3707A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330078.2:c.3731A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330082.2:c.3707A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330084.2:c.3665A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330085.2:c.3704A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330086.2:c.3731A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330091.2:c.626A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330092.2:c.626A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330093.2:c.3728A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330094.2:c.3719A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pitt-Hopkins-like syndrome 2 (PTHSL2)
Identifiers:: MONDO: MONDO:0013690; MedGen: C3280479; Orphanet: 221150; OMIM: 614325

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180020	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 21, 2021)	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

SCV002180020

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 21, 2021)

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

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002180020.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NRXN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 1284 of the NRXN1 protein (p.Asn1284Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine.

#	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: Sep 29, 2024

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