NM_018941.4(CLN8):c.680A>T (p.Tyr227Phe) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 24, 2022
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:: RCV002044152.5

Allele description [Variation Report for NM_018941.4(CLN8):c.680A>T (p.Tyr227Phe)]

NM_018941.4(CLN8):c.680A>T (p.Tyr227Phe)

Gene:

CLN8:CLN8 transmembrane ER and ERGIC protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.3

Genomic location:

Preferred name:

NM_018941.4(CLN8):c.680A>T (p.Tyr227Phe)

HGVS:

NC_000008.11:g.1780386A>T
NG_008656.2:g.29609A>T
NM_018941.4:c.680A>TMANE SELECT
NP_061764.2:p.Tyr227Phe
LRG_691:g.29609A>T
NC_000008.10:g.1728552A>T

Protein change:

Y227F

Links:

dbSNP: rs368561820

NCBI 1000 Genomes Browser:

rs368561820

Molecular consequence:

NM_018941.4:c.680A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis
Synonyms:: Ceroid storage disease
Identifiers:: MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

Recent activity

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PREDICTED: Homo sapiens HERPUD family member 2 (HERPUD2), transcript variant X2,...
PREDICTED: Homo sapiens HERPUD family member 2 (HERPUD2), transcript variant X2, mRNA
gi|2217368102|ref|XM_047420698.1|

Nucleotide
homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain mem...
homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 2 protein isoform X1 [Homo sapiens]
gi|2462615642|ref|XP_054214760.1|

Protein
plasma membrane calcium-transporting ATPase 1 isoform X1 [Homo sapiens]
plasma membrane calcium-transporting ATPase 1 isoform X1 [Homo sapiens]
gi|2217289212|ref|XP_047284845.1|

Protein
secreted frizzled-related protein 1 [Prionailurus viverrinus]
secreted frizzled-related protein 1 [Prionailurus viverrinus]
gi|2228810717|ref|XP_047712525.1|

Protein
TLS: Enterobacterales bacterium endosymbiont of Trioza cinnamomi gene for 16S ri...
TLS: Enterobacterales bacterium endosymbiont of Trioza cinnamomi gene for 16S ribosomal RNA, partial sequence, tri_sv4
gi|2624484880|dbj|TAAC01000007.1||g S:TAAC01|tri_sv4

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002111715	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 24, 2022)	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

SCV002111715

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 24, 2022)

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, SCV002111715.2

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 227 of the CLN8 protein (p.Tyr227Phe). This variant is present in population databases (rs368561820, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CLN8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1348111). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CLN8 protein function. 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.

#	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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