rs1078005

Positions:

• chr2-85542123-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005911.6(MAT2A):​c.550-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,591,112 control chromosomes in the GnomAD database, including 774,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74766 hom., cov: 33)
  • Exomes 𝑓: 0.99 (700077 hom.)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.197

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]

MAT2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-85542123-G-A is Benign according to our data. Variant chr2-85542123-G-A is described in ClinVar as [Benign]. Clinvar id is 674698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.550-32G>A		intron_variant		ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.550-32G>A		intron_variant		1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000409017.1	c.361-32G>A		intron_variant		1		ENSP00000386353.1
MAT2A	ENST00000481412.5	n.528-32G>A		intron_variant		1
MAT2A	ENST00000490878.1	n.559G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150826 AN: 152266 Hom.: 74708 Cov.: 33

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.985

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.995

GnomAD3 exomes AF: 0.989 AC: 248117 AN: 250934 Hom.: 122676 AF XY: 0.988 AC XY: 134020 AN XY: 135602

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.973

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.994

Gnomad FIN exome AF: 0.985

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.986 AC: 1419279 AN: 1438728 Hom.: 700077 Cov.: 26 AF XY: 0.987 AC XY: 706935 AN XY: 716452

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 0.973

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.985

Gnomad4 NFE exome AF: 0.985

Gnomad4 OTH exome AF: 0.988

GnomAD4 genome AF: 0.991 AC: 150943 AN: 152384 Hom.: 74766 Cov.: 33 AF XY: 0.991 AC XY: 73842 AN XY: 74532

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.995

Alfa AF: 0.987 Hom.: 13771

Bravo AF: 0.992

Asia WGS AF: 0.999 AC: 3476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.86
CADD	Benign	1.9
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1078005; hg19: chr2-85769246;