rs886037646
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_004752.4(GCM2):c.893del(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
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 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 4 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
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| GCM2 | NM_004752.4 | c.893del | p.Ile298ThrfsTer10 | frameshift_variant | 5/5 | ENST00000379491.5 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GCM2 | ENST00000379491.5 | c.893del | p.Ile298ThrfsTer10 | frameshift_variant | 5/5 | 1 | NM_004752.4 | P1 |
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
GnomAD4 exome
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1461824
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32
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727214
Gnomad4 AFR exome
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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
| Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 2010 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at