rs6733827

Positions:

• chr2-85539156-G-A
• chr2-85539156-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The 2-85539156-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 667,154 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (22 hom., cov: 33)
  • Exomes 𝑓: 0.00081 (4 hom.)
• Consequence: MAT2A ENST00000306434.8 upstream_gene
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

Genes affected

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-85539156-G-A is Benign according to our data. Variant chr2-85539156-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 679475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00826 (1257/152194) while in subpopulation AFR AF= 0.0282 (1173/41542). AF 95% confidence interval is 0.0269. There are 22 homozygotes in gnomad4. There are 607 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1257 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT2A	NM_005911.6			upstream_gene_variant		ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8			upstream_gene_variant		1	NM_005911.6	ENSP00000303147	P1
MAT2A	ENST00000465151.5			upstream_gene_variant		2
MAT2A	ENST00000469221.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1255 AN: 152080 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000812 AC: 418 AN: 514960 Hom.: 4 Cov.: 7 AF XY: 0.000705 AC XY: 192 AN XY: 272422

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.00281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000119

Gnomad4 SAS exome AF: 0.0000205

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00826 AC: 1257 AN: 152194 Hom.: 22 Cov.: 33 AF XY: 0.00816 AC XY: 607 AN XY: 74406

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00493 Hom.: 1

Bravo AF: 0.00965

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6733827; hg19: chr2-85766279;