NM_001365536.1(SCN9A):c.1314+1G>A AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 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:: RCV003803479.2

Allele description [Variation Report for NM_001365536.1(SCN9A):c.1314+1G>A]

NM_001365536.1(SCN9A):c.1314+1G>A

Genes:

SCN1A-AS1:SCN1A and SCN9A antisense RNA 1 [Gene - HGNC]
SCN9A:sodium voltage-gated channel alpha subunit 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001365536.1(SCN9A):c.1314+1G>A

HGVS:

NC_000002.12:g.166288436C>T
NG_012798.1:g.92552G>A
NM_001365536.1:c.1314+1G>AMANE SELECT
NM_002977.4:c.1314+1G>A
LRG_369:g.92552G>A
NC_000002.11:g.167144946C>T

Molecular consequence:

NM_001365536.1:c.1314+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_002977.4:c.1314+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Neuropathy, hereditary sensory and autonomic, type 2A (HSAN2A)
Synonyms:: ACROOSTEOLYSIS, GIACCAI TYPE; ACROOSTEOLYSIS, NEUROGENIC; HSAN IIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024309; MedGen: C2752089; Orphanet: 970; OMIM: 201300

Name:: Generalized epilepsy with febrile seizures plus, type 7 (GEFSP7)
Synonyms:: GEFS+, TYPE 7
Identifiers:: MONDO: MONDO:0013470; MedGen: C2751778; Orphanet: 36387; OMIM: 613863

Recent activity

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Hydrolagus colliei isolate sHydCol1 chromosome 16, whole genome shotgun sequence
Hydrolagus colliei isolate sHydCol1 chromosome 16, whole genome shotgun sequence
gi|2645211556|gb|CM068797.1||gnl|WG JKX|SUPER_16

Nucleotide
Hydrolagus colliei isolate sHydCol1 chromosome 4, whole genome shotgun sequence
Hydrolagus colliei isolate sHydCol1 chromosome 4, whole genome shotgun sequence
gi|2645211568|gb|CM068785.1||gnl|WG JKX|SUPER_4

Nucleotide
Homo sapiens transcription factor B1, mitochondrial (TFB1M), RefSeqGene on chrom...
Homo sapiens transcription factor B1, mitochondrial (TFB1M), RefSeqGene on chromosome 6; nuclear gene for mitochondrial product
gi|1187443750|ref|NG_027528.2|

Nucleotide
Synthetic construct Mus musculus clone IMAGE:100061670, MGC:190273 regulatory fa...
Synthetic construct Mus musculus clone IMAGE:100061670, MGC:190273 regulatory factor X, 7 (Rfx7) mRNA, encodes complete protein
gi|162319107|gb|BC156261.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004592118	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 23, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 17470132, 19304393, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004592118

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 23, 2023)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.

Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, et al.

Clin Genet. 2007 Apr;71(4):311-9.

PubMed [citation]

PMID:: 17470132

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004592118.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects a donor splice site in intron 10 of the SCN9A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN9A are known to be pathogenic (PMID: 17470132, 19304393). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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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