NM_004752.4:c.893delT
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_004752.4(GCM2):c.893delT(p.Ile298ThrfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
GCM2
NM_004752.4 frameshift
NM_004752.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.20
Publications
3 publications found
Genes affected
GCM2 (HGNC:4198): (glial cells missing transcription factor 2) This gene is a homolog of the Drosophila glial cells missing gene, which is thought to act as a binary switch between neuronal and glial cell determination. The protein encoded by this gene contains a conserved N-terminal GCM motif that has DNA-binding activity. The protein is a transcription factor that acts as a master regulator of parathyroid development. It has been suggested that this transcription factor might mediate the effect of calcium on parathyroid hormone expression and secretion in parathyroid cells. Mutations in this gene are associated with hypoparathyroidism. [provided by RefSeq, Jul 2008]
GCM2 Gene-Disease associations (from GenCC):
- hypoparathyroidism, familial isolated, 2Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- familial isolated hyperparathyroidismInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial isolated hypoparathyroidism due to agenesis of parathyroid glandInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hyperparathyroidism 4Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-10874622-GA-G is Pathogenic according to our data. Variant chr6-10874622-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 64623.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GCM2 | ENST00000379491.5 | c.893delT | p.Ile298ThrfsTer10 | frameshift_variant | Exon 5 of 5 | 1 | NM_004752.4 | ENSP00000368805.4 | ||
ENSG00000272162 | ENST00000480294.1 | n.101-16890delA | intron_variant | Intron 3 of 18 | 2 | ENSP00000417929.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727214 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461824
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
727214
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
4
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111952
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
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>80
Age
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypoparathyroidism, familial isolated, 2 Pathogenic:1
May 15, 2010
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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