chr2-85553008-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000821.7(GGCX):c.1218C>T(p.Arg406Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.276 in 1,613,452 control chromosomes in the GnomAD database, including 62,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6889 hom., cov: 32)

Exomes 𝑓: 0.27 ( 56071 hom. )

Consequence

GGCX
NM_000821.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.58

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
vitamin K-dependent clotting factors, combined deficiency of, type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
pulmonary arterial hypertension
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GGCX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 2-85553008-G-A is Benign according to our data. Variant chr2-85553008-G-A is described in ClinVar as Benign. ClinVar VariationId is 337266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000821.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGCX	NM_000821.7	MANE Select	c.1218C>T	p.Arg406Arg	synonymous	Exon 9 of 15	NP_000812.2
	GGCX	NM_001142269.4		c.1047C>T	p.Arg349Arg	synonymous	Exon 8 of 14	NP_001135741.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GGCX	ENST00000233838.9	TSL:1 MANE Select	c.1218C>T	p.Arg406Arg	synonymous	Exon 9 of 15	ENSP00000233838.3
GGCX	ENST00000911478.1		c.1218C>T	p.Arg406Arg	synonymous	Exon 9 of 15	ENSP00000581537.1
GGCX	ENST00000896458.1		c.1218C>T	p.Arg406Arg	synonymous	Exon 9 of 15	ENSP00000566517.1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44973

AN:

151912

Hom.:

6877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.262

AC:

65780

AN:

251446

AF XY:

0.259

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.274

AC:

400715

AN:

1461422

Hom.:

56071

Cov.:

AF XY:

0.271

AC XY:

197245

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.355

AC:

11898

AN:

33472

American (AMR)

AF:

0.196

AC:

8752

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6168

AN:

26136

East Asian (EAS)

AF:

0.313

AC:

12410

AN:

39696

South Asian (SAS)

AF:

0.168

AC:

14494

AN:

86254

European-Finnish (FIN)

AF:

0.301

AC:

16054

AN:

53420

Middle Eastern (MID)

AF:

0.212

AC:

1221

AN:

5768

European-Non Finnish (NFE)

AF:

0.282

AC:

313224

AN:

1111590

Other (OTH)

AF:

0.273

AC:

16494

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17353

34707

52060

69414

86767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10462

20924

31386

41848

52310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.296

AC:

45010

AN:

152030

Hom.:

6889

Cov.:

AF XY:

0.294

AC XY:

21847

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.360

AC:

14941

AN:

41460

American (AMR)

AF:

0.224

AC:

3422

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

757

AN:

3472

East Asian (EAS)

AF:

0.325

AC:

1677

AN:

5164

South Asian (SAS)

AF:

0.168

AC:

812

AN:

4824

European-Finnish (FIN)

AF:

0.320

AC:

3380

AN:

10566

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19042

AN:

67966

Other (OTH)

AF:

0.280

AC:

590

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1648

3296

4945

6593

8241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.288

Hom.:

11586

Bravo

AF:

0.295

Asia WGS

AF:

0.278

AC:

967

AN:

3478

EpiCase

AF:

0.274

EpiControl

AF:

0.273

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Vitamin K-dependent clotting factors, combined deficiency of, type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.1

(source)

DANN

Benign

0.55

PhyloP100

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over