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

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 30, 2021
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:: RCV000764442.15

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]

Condition(s)

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

Name:: Chromosome 2p16.3 deletion syndrome
Identifiers:: MONDO: MONDO:0013696; MedGen: C3808494; OMIM: 614332

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000895499	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002047665	GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies	no classification provided	not provided	unknown	phenotyping only
SCV002495880	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 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

SCV000895499

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 31, 2018)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002047665

GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies

no classification provided

not provided

unknown

phenotyping only

SCV002495880

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, phenotyping only

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

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000895499.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies, SCV002047665.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

Variant interpreted as Uncertain significance and reported on 07-13-2019 by lab or GTR ID 26957. GenomeConnect - Association for Creatine Deficiencies assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV002495880.2

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

Description

NRXN1 NM_001135659.2 exon 15 p.His885Tyr (c.2653C>T): This variant has been reported in the literature in at least 1 individual with autism spectrum disorder (ASD), segregating with disease in 1 affected family member. However, this family member did not meet clinical criteria for ASD (Jiang 2013 PMID:23849776). This variant is present in 0.1% (78/68024) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-50497679-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:20245). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	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 13, 2025

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