Genetic Variant GCM2:c.90+887A>G (chr6-10880817-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004752.4(GCM2):c.90+887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,270 control chromosomes in the GnomAD database, including 70,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.96 ( 70946 hom., cov: 32)

Consequence

GCM2
NM_004752.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

1 publications found

Variant links:

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, 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial isolated hyperparathyroidism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated hypoparathyroidism due to agenesis of parathyroid gland
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hyperparathyroidism 4
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GCM2 links:

ENSG00000272162 (HGNC:):

ENSG00000272162 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM2	NM_004752.4 link	c.90+887A>G		intron_variant	Intron 1 of 4	ENST00000379491.5	NP_004743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCM2	ENST00000379491.5 link	c.90+887A>G		intron_variant	Intron 1 of 4	1	NM_004752.4	ENSP00000368805.4
ENSG00000272162	ENST00000480294.1 link	n.101-10696T>C		intron_variant	Intron 3 of 18	2		ENSP00000417929.1

Frequencies

GnomAD3 genomes

AF:

0.964

AC:

146653

AN:

152152

Hom.:

70913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.975

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.964

AC:

146742

AN:

152270

Hom.:

70946

Cov.:

AF XY:

0.965

AC XY:

71853

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.875

AC:

36334

AN:

41522

American (AMR)

AF:

0.987

AC:

15094

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3471

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5188

AN:

5188

South Asian (SAS)

AF:

0.999

AC:

4817

AN:

4820

European-Finnish (FIN)

AF:

0.998

AC:

10595

AN:

10620

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67977

AN:

68034

Other (OTH)

AF:

0.975

AC:

2060

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

248

496

745

993

1241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.962

Hom.:

11101

Bravo

AF:

0.958

Asia WGS

AF:

0.991

AC:

3447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.0

(source)

DANN

Benign

0.37

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over