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NC_000002.12:g.(?_165090130)_(166286643_?)del AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 2020
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:
RCV001387894.5

Allele description [Variation Report for NC_000002.12:g.(?_165090130)_(166286643_?)del]

NC_000002.12:g.(?_165090130)_(166286643_?)del

Genes:
  • LOC129935044:ATAC-STARR-seq lymphoblastoid active region 16726 [Gene]
  • LOC129935045:ATAC-STARR-seq lymphoblastoid active region 16727 [Gene]
  • LOC129935046:ATAC-STARR-seq lymphoblastoid active region 16728 [Gene]
  • LOC129935047:ATAC-STARR-seq lymphoblastoid active region 16729 [Gene]
  • LOC129935043:ATAC-STARR-seq lymphoblastoid silent region 12066 [Gene]
  • LOC126806396:BRD4-independent group 4 enhancer GRCh37_chr2:166317128-166318327 [Gene]
  • LOC129388938:MPRA-validated peak3912 silencer [Gene]
  • SCN1A-AS1:SCN1A and SCN9A antisense RNA 1 [Gene - HGNC]
  • LOC120977013:Sharpr-MPRA regulatory region 13511 [Gene]
  • TTC21B-AS1:TTC21B antisense RNA 1 [Gene - HGNC]
  • CSRNP3:cysteine and serine rich nuclear protein 3 [Gene - OMIM - HGNC]
  • GALNT3:polypeptide N-acetylgalactosaminyltransferase 3 [Gene - OMIM - HGNC]
  • SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
  • SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]
  • SCN3A:sodium voltage-gated channel alpha subunit 3 [Gene - OMIM - HGNC]
  • SCN9A:sodium voltage-gated channel alpha subunit 9 [Gene - OMIM - HGNC]
  • TTC21B:tetratricopeptide repeat domain 21B [Gene - OMIM - HGNC]
  • LOC100506124:uncharacterized LOC100506124 [Gene]
  • LOC102724058:uncharacterized LOC102724058 [Gene]
Variant type:
Deletion
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NC_000002.12:g.(?_165090130)_(166286643_?)del
HGVS:
  • NC_000002.12:g.(?_165090130)_(166286643_?)del
  • NC_000002.11:g.(?_165946640)_(167143153_?)del

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001588634Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 1, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Null mutation in SCN9A in which noxious stimuli can be detected in the absence of pain.

Ramirez JD, Habib AM, Cox JJ, Themistocleous AC, McMahon SB, Wood JN, Bennett DL.

Neurology. 2014 Oct 21;83(17):1577-80. doi: 10.1212/WNL.0000000000000913. Epub 2014 Sep 24. No abstract available.

PubMed [citation]
PMID:
25253744
PMCID:
PMC4222855

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, SCV001588634.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SCN9A protein. Other variant(s) that disrupt this region (p.Glu1773Glyfs*14) have been determined to be pathogenic (PMID: 25253744, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with SCN9A-related disease. This variant is a gross deletion of the genomic region encompassing exons 11 to 27 of the SCN9A gene. The 5' boundary is likely confined to intron 10. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024