NM_000266.4(NDP):c.269G>A (p.Arg90His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 2024
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:: RCV004526061.2

Allele description [Variation Report for NM_000266.4(NDP):c.269G>A (p.Arg90His)]

NM_000266.4(NDP):c.269G>A (p.Arg90His)

Genes:

NDP-AS1:NDP antisense RNA 1 [Gene - HGNC]
NDP:norrin cystine knot growth factor NDP [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.3

Genomic location:

Preferred name:

NM_000266.4(NDP):c.269G>A (p.Arg90His)

HGVS:

NC_000023.11:g.43949932C>T
NG_009832.1:g.28744G>A
NM_000266.4:c.269G>AMANE SELECT
NP_000257.1:p.Arg90His
NC_000023.10:g.43809178C>T
NM_000266.3:c.269G>A
NR_046631.1:n.201C>T

Protein change:

R90H

Links:

dbSNP: rs104894867

NCBI 1000 Genomes Browser:

rs104894867

Molecular consequence:

NM_000266.4:c.269G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_046631.1:n.201C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005039487	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 29, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31456290, 34582765 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005039487

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 29, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

Sharon D, Ben-Yosef T, Goldenberg-Cohen N, Pras E, Gradstein L, Soudry S, Mezer E, Zur D, Abbasi AH, Zeitz C, Cremers FPM, Khan MI, Levy J, Rotenstreich Y, Birk OS, Ehrenberg M, Leibu R, Newman H, Shomron N, Banin E, Perlman I.

Hum Mutat. 2020 Jan;41(1):140-149. doi: 10.1002/humu.23903. Epub 2019 Sep 15.

PubMed [citation]

PMID:: 31456290

Severe Exudative Vitreoretinopathy as a Common Feature for CTNNB1, KIF11 and NDP Variants Plus Sector Degeneration for KIF11.

Yang J, Xiao X, Li S, Mai G, Jia X, Wang P, Sun W, Zhang Q.

Am J Ophthalmol. 2022 Mar;235:178-187. doi: 10.1016/j.ajo.2021.09.017. Epub 2021 Sep 25.

PubMed [citation]

PMID:: 34582765

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005039487.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: NDP c.269G>A (p.Arg90His) results in a non-conservative amino acid change located in the Cystine knot, C-terminal (IPR006207) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.6e-05 in 1205187 control chromosomes, including 20 hemizygotes (gnomAD database v4.0.0), suggesting a benign role for the variant. c.269G>A has been reported in the literature in individuals affected with Norrie disease (Sharon_2020) and Vitreoretinopathy (Yang_2022). These reports do not provide unequivocal conclusions about association of the variant with Atrophia bulborum hereditaria. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31456290, 34582765). ClinVar contains an entry for this variant (Variation ID: 812352). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Jul 7, 2024

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