NM_000157.4(GBA1):c.232C>T (p.Arg78Cys) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 15, 2023
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:: RCV003155523.4

Allele description [Variation Report for NM_000157.4(GBA1):c.232C>T (p.Arg78Cys)]

NM_000157.4(GBA1):c.232C>T (p.Arg78Cys)

Genes:

LOC106627981:GBA recombination region [Gene]
GBA1:glucosylceramidase beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_000157.4(GBA1):c.232C>T (p.Arg78Cys)

HGVS:

NC_000001.11:g.155239961G>A
NG_009783.1:g.9737C>T
NG_042867.1:g.6423G>A
NM_000157.4:c.232C>TMANE SELECT
NM_001005741.2:c.232C>T
NM_001005741.3:c.232C>T
NM_001005742.3:c.232C>T
NM_001171811.2:c.-30C>T
NM_001171812.2:c.232C>T
NP_000148.2:p.Arg78Cys
NP_001005741.1:p.Arg78Cys
NP_001005742.1:p.Arg78Cys
NP_001165283.1:p.Arg78Cys
NC_000001.10:g.155209752G>A
NM_000157.4:c.232C>T
NM_001005742.2:c.232C>T

Protein change:

R78C

Molecular consequence:

NM_001171811.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000157.4:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.232C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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motile sperm domain-containing protein 2 isoform 2 [Homo sapiens]
motile sperm domain-containing protein 2 isoform 2 [Homo sapiens]
gi|294489346|ref|NP_001170946.1|

Protein
Homo sapiens motile sperm domain containing 2 (MOSPD2), transcript variant 2, mR...
Homo sapiens motile sperm domain containing 2 (MOSPD2), transcript variant 2, mRNA
gi|294489345|ref|NM_001177475.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003713633	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 28, 2022)	germline	clinical testing	Citation Link,
SCV003844774	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 15, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003713633

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 28, 2022)

germline

clinical testing

Citation Link,

SCV003844774

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 15, 2023)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV003713633.2

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

Description

The c.232C>T (p.R78C) alteration is located in exon 4 (coding exon 3) of the GBA gene. This alteration results from a C to T substitution at nucleotide position 232, causing the arginine (R) at amino acid position 78 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844774.1

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

Description

Variant summary: GBA c.232C>T (p.Arg78Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.2e-05 in 251336 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in GBA causing Gaucher Disease (9.2e-05 vs 0.005), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.232C>T in individuals affected with Gaucher Disease and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as uncertain significance. Based on the evidence outlined above, the variant was classified as 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

Last Updated: Nov 3, 2024

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