Variant chr2-85550510-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000821.7(GGCX):c.2084+45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,425,082 control chromosomes in the GnomAD database, including 5,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 393 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5361 hom. )

Consequence

GGCX
NM_000821.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.840

Variant links:

Genes affected

GGCX (HGNC:4247): (gamma-glutamyl carboxylase) This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

GGCX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-85550510-C-G is Benign according to our data. Variant chr2-85550510-C-G is described in ClinVar as [Benign]. Clinvar id is 375657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGCX	NM_000821.7 linkuse as main transcript	c.2084+45G>C		intron_variant		ENST00000233838.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGCX	ENST00000233838.9 linkuse as main transcript	c.2084+45G>C		intron_variant		1	NM_000821.7	P1	P38435-1

Frequencies

GnomAD3 genomes

AF:

0.0587

AC:

8924

AN:

152136

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0585

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0981

Gnomad OTH

AF:

0.0473

GnomAD3 exomes

AF:

0.0573

AC:

14316

AN:

249774

Hom.:

560

AF XY:

0.0572

AC XY:

7740

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0194

Gnomad FIN exome

AF:

0.0606

Gnomad NFE exome

AF:

0.0930

Gnomad OTH exome

AF:

0.0534

GnomAD4 exome

AF:

0.0858

AC:

109174

AN:

1272828

Hom.:

5361

Cov.:

AF XY:

0.0831

AC XY:

53374

AN XY:

642450

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0290

Gnomad4 ASJ exome

AF:

0.0419

Gnomad4 EAS exome

AF:

0.0000772

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0614

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0694

GnomAD4 genome

AF:

0.0586

AC:

8923

AN:

152254

Hom.:

393

Cov.:

AF XY:

0.0541

AC XY:

4030

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0585

Gnomad4 NFE

AF:

0.0980

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0721

Hom.:

Bravo

AF:

0.0547

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

GGCX-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 22, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over