chr2-85544938-AT-A

Variant names:

• chr2-85544938-AT-A
• rs886056355
• NM_000821.7:c.*4995delA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_000821.7(GGCX):​c.*4995delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 147,068 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGCX NM_000821.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000462 (68/147068) while in subpopulation SAS AF= 0.000647 (3/4636). AF 95% confidence interval is 0.000389. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGCX	NM_000821.7	c.*4995delA		3_prime_UTR_variant	Exon 15 of 15	ENST00000233838.9	NP_000812.2
MAT2A	NM_005911.6	c.*1178delT		3_prime_UTR_variant	Exon 9 of 9	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGCX	ENST00000233838	c.*4995delA		3_prime_UTR_variant	Exon 15 of 15	1	NM_000821.7	ENSP00000233838.3
MAT2A	ENST00000306434.8	c.*1178delT		3_prime_UTR_variant	Exon 9 of 9	1	NM_005911.6	ENSP00000303147.3

Frequencies

GnomAD3 genomes AF: 0.000463 AC: 68 AN: 147002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000645

Gnomad FIN AF: 0.00159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000287

Gnomad OTH AF: 0.000499

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0327 AC: 11 AN: 336 Hom.: 0 Cov.: 0 AF XY: 0.0409 AC XY: 9 AN XY: 220

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000462 AC: 68 AN: 147068 Hom.: 0 Cov.: 32 AF XY: 0.000559 AC XY: 40 AN XY: 71560

Gnomad4 AFR AF: 0.000570

Gnomad4 AMR AF: 0.000340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000399

Gnomad4 SAS AF: 0.000647

Gnomad4 FIN AF: 0.00159

Gnomad4 NFE AF: 0.000287

Gnomad4 OTH AF: 0.000496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs886056355; hg19: chr2-85772061;