NM_001287.6(CLCN7):c.1841T>G (p.Leu614Arg) AND Autosomal dominant osteopetrosis 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 17, 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:: RCV001255865.1

Allele description [Variation Report for NM_001287.6(CLCN7):c.1841T>G (p.Leu614Arg)]

NM_001287.6(CLCN7):c.1841T>G (p.Leu614Arg)

Gene:

CLCN7:chloride voltage-gated channel 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001287.6(CLCN7):c.1841T>G (p.Leu614Arg)

HGVS:

NC_000016.10:g.1448723A>C
NG_007567.1:g.31362T>G
NM_001114331.3:c.1769T>G
NM_001287.6:c.1841T>GMANE SELECT
NP_001107803.1:p.Leu590Arg
NP_001278.1:p.Leu614Arg
NC_000016.9:g.1498724A>C

Protein change:

L590R

Links:

dbSNP: rs1064794323

NCBI 1000 Genomes Browser:

rs1064794323

Molecular consequence:

NM_001114331.3:c.1769T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001287.6:c.1841T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Autosomal dominant osteopetrosis 2
Synonyms:: ALBERS-SCHONBERG DISEASE, AUTOSOMAL DOMINANT; MARBLE BONES, AUTOSOMAL DOMINANT; OSTEOSCLEROSIS FRAGILIS GENERALISATA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008156; MedGen: C3179239; Orphanet: 53; OMIM: 166600

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Homo sapiens ribosomal protein L3-like, mRNA (cDNA clone MGC:54082 IMAGE:6204847...
Homo sapiens ribosomal protein L3-like, mRNA (cDNA clone MGC:54082 IMAGE:6204847), complete cds
gi|30046541|gb|BC050413.1|

Nucleotide
171070[uid] AND (alive[prop]) (1)
Gene
Ptpn21 protein tyrosine phosphatase, non-receptor type 21 [Rattus norvegicus]
Ptpn21 protein tyrosine phosphatase, non-receptor type 21 [Rattus norvegicus]
Gene ID:171070

Gene
Homologene neighbors for GEO Profiles (Select 71243758) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001190007	Bioinformatics Research Center, Pavlov First St. Petersburg State Medical University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 17, 2020)	unknown	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

SCV001190007

Bioinformatics Research Center, Pavlov First St. Petersburg State Medical University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 17, 2020)

unknown

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
Russian	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Bioinformatics Research Center, Pavlov First St. Petersburg State Medical University, SCV001190007.1

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

Description

The c.T1769G (p.Leu614Arg) is novel and has not been reported in the 1000 Genomes Project build 20130502 (2,504 samples, accessed 9/18/2019), dpSNP build 153 (accessed 9/18/2019), or Exome Aggregation Consortium (ExAC, 60,706 samples, accessed 9/18/2019) database. A different mutation in the same position was reported in ClinVar database (rs1064794323 - Leu614Pro) in a child with severe osteopetrosis, anemia, blindness, neurological impairment and macrocephaly, who died at 4 years of age, and also had a deletion in exon 17 of the CLCN7 gene (Frattini et al., 2003).

#	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		1	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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