NM_014844.5(TECPR2):c.818G>A (p.Arg273His) AND Hereditary spastic paraplegia 49

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Aug 23, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001239107.7

Allele description [Variation Report for NM_014844.5(TECPR2):c.818G>A (p.Arg273His)]

NM_014844.5(TECPR2):c.818G>A (p.Arg273His)

Gene:

TECPR2:tectonin beta-propeller repeat containing 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.31

Genomic location:

Preferred name:

NM_014844.5(TECPR2):c.818G>A (p.Arg273His)

HGVS:

NC_000014.9:g.102425158G>A
NG_042851.1:g.67247G>A
NM_001172631.3:c.818G>A
NM_014844.5:c.818G>AMANE SELECT
NP_001166102.1:p.Arg273His
NP_055659.2:p.Arg273His
NC_000014.8:g.102891495G>A
NC_000014.8:g.102891495G>A
NM_014844.3:c.818G>A
NM_014844.4:c.818G>A

Protein change:

R273H

Links:

dbSNP: rs144069125

NCBI 1000 Genomes Browser:

rs144069125

Molecular consequence:

NM_001172631.3:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014844.5:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary spastic paraplegia 49 (HSAN9)
Synonyms:: Spastic paraplegia 49, autosomal recessive; NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IX, WITH DEVELOPMENTAL DELAY
Identifiers:: MONDO: MONDO:0014016; MedGen: C3542549; Orphanet: 320385; OMIM: 615031

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001411957	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001522279	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 5, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002087998	Natera, Inc.	no assertion criteria provided	Uncertain significance (Dec 9, 2019)	germline	clinical testing
SCV002780954	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 15, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001411957.2

#	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 arginine, which is basic and polar, with histidine, which is basic and polar, at codon 273 of the TECPR2 protein (p.Arg273His). This variant is present in population databases (rs144069125, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 964805). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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

From Baylor Genetics, SCV001522279.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002087998.1

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

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002780954.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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