chr2-85545355-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000821.7(GGCX):​c.*4579G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,678 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 37 hom., cov: 32)
Exomes 𝑓: 0.060 ( 0 hom. )

Consequence

GGCX
NM_000821.7 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0240
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]
MAT2A (HGNC:6904): (methionine adenosyltransferase 2A) The protein encoded by this gene catalyzes the production of S-adenosylmethionine (AdoMet) from methionine and ATP. AdoMet is the key methyl donor in cellular processes. [provided by RefSeq, Jun 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-85545355-C-T is Benign according to our data. Variant chr2-85545355-C-T is described in ClinVar as [Benign]. Clinvar id is 337176.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAdExome4 highest population allele frequency = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGCXNM_000821.7 linkc.*4579G>A 3_prime_UTR_variant Exon 15 of 15 ENST00000233838.9 NP_000812.2 P38435-1
MAT2ANM_005911.6 linkc.*1583C>T downstream_gene_variant ENST00000306434.8 NP_005902.1 P31153-1A0A140VJP5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGCXENST00000233838 linkc.*4579G>A 3_prime_UTR_variant Exon 15 of 15 1 NM_000821.7 ENSP00000233838.3 P38435-1
MAT2AENST00000306434.8 linkc.*1583C>T downstream_gene_variant 1 NM_005911.6 ENSP00000303147.3 P31153-1

Frequencies

GnomAD3 genomes
AF:
0.0182
AC:
2776
AN:
152124
Hom.:
37
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00476
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.0288
Gnomad ASJ
AF:
0.0190
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.0153
Gnomad FIN
AF:
0.0411
Gnomad MID
AF:
0.0380
Gnomad NFE
AF:
0.0219
Gnomad OTH
AF:
0.0206
GnomAD4 exome
AF:
0.0596
AC:
26
AN:
436
Hom.:
0
Cov.:
0
AF XY:
0.0682
AC XY:
18
AN XY:
264
show subpopulations
Gnomad4 FIN exome
AF:
0.0590
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.167
GnomAD4 genome
AF:
0.0182
AC:
2777
AN:
152242
Hom.:
37
Cov.:
32
AF XY:
0.0185
AC XY:
1374
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00474
Gnomad4 AMR
AF:
0.0288
Gnomad4 ASJ
AF:
0.0190
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.0157
Gnomad4 FIN
AF:
0.0411
Gnomad4 NFE
AF:
0.0219
Gnomad4 OTH
AF:
0.0204
Alfa
AF:
0.0144
Hom.:
4
Bravo
AF:
0.0163
Asia WGS
AF:
0.0110
AC:
37
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Vitamin K-dependent clotting factors, combined deficiency of, type 1 Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.6
DANN
Benign
0.65

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.

Other links and lift over

dbSNP: rs138686161; hg19: chr2-85772478; API