2-85556005-T-G

Position:

• chr2-85556005-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000821.7(GGCX):​c.618+177A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,038 control chromosomes in the GnomAD database, including 21,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (21002 hom., cov: 32)
• Consequence: GGCX NM_000821.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-85556005-T-G is Benign according to our data. Variant chr2-85556005-T-G is described in ClinVar as [Benign]. Clinvar id is 1221805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGCX	NM_000821.7	c.618+177A>C		intron_variant		ENST00000233838.9	NP_000812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGCX	ENST00000233838.9	c.618+177A>C		intron_variant		1	NM_000821.7	ENSP00000233838.3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77941 AN: 151920 Hom.: 20965 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.513 AC: 78033 AN: 152038 Hom.: 21002 Cov.: 32 AF XY: 0.509 AC XY: 37856 AN XY: 74302

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.508

Alfa AF: 0.421 Hom.: 2698

Bravo AF: 0.517

Asia WGS AF: 0.438 AC: 1526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.9
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs6738645; hg19: chr2-85783128;