NM_000266.4(NDP):c.269_273dup (p.Ser92fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2023
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:: RCV002872097.3

Allele description [Variation Report for NM_000266.4(NDP):c.269_273dup (p.Ser92fs)]

NM_000266.4(NDP):c.269_273dup (p.Ser92fs)

Genes:

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

Variant type:

Duplication

Cytogenetic location:

Xp11.3

Genomic location:

Preferred name:

NM_000266.4(NDP):c.269_273dup (p.Ser92fs)

HGVS:

NC_000023.11:g.43949932_43949936dup
NG_009832.1:g.28744_28748dup
NG_146867.1:g.624_628dup
NG_146868.1:g.106_110dup
NM_000266.4:c.269_273dupMANE SELECT
NP_000257.1:p.Ser92fs
NC_000023.10:g.43809173_43809174insGGAAC
NC_000023.10:g.43809178_43809182dup
NR_046631.1:n.201_205dup

Protein change:

S92fs

Molecular consequence:

NM_000266.4:c.269_273dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_046631.1:n.201_205dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003234183	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25711638, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003234183

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (2)
[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

Next-generation sequencing and novel variant determination in a cohort of 92 familial exudative vitreoretinopathy patients.

Salvo J, Lyubasyuk V, Xu M, Wang H, Wang F, Nguyen D, Wang K, Luo H, Wen C, Shi C, Lin D, Zhang K, Chen R.

Invest Ophthalmol Vis Sci. 2015 Feb 24;56(3):1937-46. doi: 10.1167/iovs.14-16065.

PubMed [citation]

PMID:: 25711638
PMCID:: PMC4365990

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, SCV003234183.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NDP protein in which other variant(s) (p.Cys131*) have been determined to be pathogenic (PMID: 25711638; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 2030965). This variant has not been reported in the literature in individuals affected with NDP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser92Valfs*14) in the NDP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the NDP protein.

#	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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