NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr) AND not provided

Germline classification:: Uncertain significance (6 submissions)
Last evaluated:: Jan 23, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000513409.41

Allele description [Variation Report for NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr)]

NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr)

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.2533C>T (p.His845Tyr)

Other names:

p.H885Y:CAT>TAT; p.His885Tyr

HGVS:

NC_000002.12:g.50497679G>A
NG_011878.1:g.539858C>T
NM_001135659.3:c.2653C>T
NM_001330077.2:c.2509C>T
NM_001330078.2:c.2533C>TMANE SELECT
NM_001330082.2:c.2509C>T
NM_001330083.2:c.2467C>T
NM_001330084.2:c.2467C>T
NM_001330085.2:c.2506C>T
NM_001330086.2:c.2533C>T
NM_001330087.2:c.2422C>T
NM_001330088.2:c.2452C>T
NM_001330093.2:c.2530C>T
NM_001330094.2:c.2521C>T
NM_001330095.2:c.2482C>T
NM_001330096.2:c.2422C>T
NM_004801.6:c.2533C>T
NP_001129131.1:p.His885Tyr
NP_001317006.1:p.His837Tyr
NP_001317007.1:p.His845Tyr
NP_001317011.1:p.His837Tyr
NP_001317012.1:p.His823Tyr
NP_001317013.1:p.His823Tyr
NP_001317014.1:p.His836Tyr
NP_001317015.1:p.His845Tyr
NP_001317016.1:p.His808Tyr
NP_001317017.1:p.His818Tyr
NP_001317022.1:p.His844Tyr
NP_001317023.1:p.His841Tyr
NP_001317024.1:p.His828Tyr
NP_001317025.1:p.His808Tyr
NP_004792.1:p.His845Tyr
NC_000002.11:g.50724817G>A
NM_001135659.1:c.2653C>T
NM_001135659.2:c.2653C>T

Protein change:

H808Y

Links:

dbSNP: rs199784139

NCBI 1000 Genomes Browser:

rs199784139

Molecular consequence:

NM_001135659.3:c.2653C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330077.2:c.2509C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330078.2:c.2533C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330082.2:c.2509C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330083.2:c.2467C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330084.2:c.2467C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330085.2:c.2506C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330086.2:c.2533C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330087.2:c.2422C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330088.2:c.2452C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330093.2:c.2530C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330094.2:c.2521C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330095.2:c.2482C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330096.2:c.2422C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004801.6:c.2533C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000241886	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 23, 2024)	germline	clinical testing	Citation Link,
SCV000608937	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2017)	germline	clinical testing	Citation Link,
SCV000704629	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Dec 14, 2016)	germline	clinical testing	Citation Link,
SCV001963022	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001966872	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002541828	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 4, 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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	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 GeneDx, SCV000241886.14

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

Description

Reported in a patient with autism spectrum disorder, sibling with learning disabilities and their unaffected father, and in an unrelated individual with spastic paraplegia and epilepsy who was also a compound heterozygote for 2 variants in the ALDH18A1 gene (PMID: 23849776, 29754261); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; This variant is associated with the following publications: (PMID: 29754261, 34168285, 23849776)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV000608937.34

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

#	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		1	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000704629.3

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

#	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		1	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001963022.1

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

#	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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001966872.1

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

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV002541828.1

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

#	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: Apr 20, 2025

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