NM_000067.3(CA2):c.275A>C (p.Gln92Pro) AND Osteopetrosis with renal tubular acidosis

Germline classification:: Likely pathogenic (1 submission)
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:: RCV001250415.1

Allele description [Variation Report for NM_000067.3(CA2):c.275A>C (p.Gln92Pro)]

NM_000067.3(CA2):c.275A>C (p.Gln92Pro)

Gene:

CA2:carbonic anhydrase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.2

Genomic location:

Preferred name:

NM_000067.3(CA2):c.275A>C (p.Gln92Pro)

HGVS:

NC_000008.11:g.85473735A>C
NG_007287.1:g.14719A>C
NM_000067.3:c.275A>CMANE SELECT
NM_001293675.2:c.49-589A>C
NP_000058.1:p.Gln92Pro
NC_000008.10:g.86385964A>C
p.Q92P

Protein change:

Q92P

Links:

dbSNP: rs1304160279

NCBI 1000 Genomes Browser:

rs1304160279

Molecular consequence:

NM_001293675.2:c.49-589A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000067.3:c.275A>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functionally_abnormal [Sequence Ontology: SO:0002218]

Observations:

Condition(s)

Name:: Osteopetrosis with renal tubular acidosis (OPTB3)
Synonyms:: Autosomal recessive osteopetrosis type 3; Guibaud Vainsel syndrome; Marble brain disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009818; MedGen: C0345407; Orphanet: 2785; OMIM: 259730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001364072	Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV001364072

Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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	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 Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, SCV001364072.1

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

Description

The index patient has a homozygous missense mutation at position 275 on the cDNA level of the CA2 gene, which leads to the exchange of the amino acid glutamic acid to proline at position 92 on the protein level. The co-segregation analysis showed that the clinically affected brother carries the sequence variant also in a homozygous state and the healthy parents are each heterozygous carriers. Several prediction programs classify this amino acid exchange as pathogenic (PP3). The sequence variant is not listed in the databases ExAC and gnomAD (PM2). The above sequence variant has already been described in three patients with osteopetrosis and renal acidosis (MIM# 259739) in homozygous state (PP5) (Hu et al. 1997; Shah et al. 2004). According to the current state of knowledge, this is a probable pathogenic mutation (class IV).

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

Last Updated: Apr 23, 2022

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