2-85539295-G-A

Variant names:

• chr2-85539295-G-A
• rs1691387581
• NM_005911.6:c.8G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005911.6(MAT2A):​c.8G>A​(p.Gly3Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAT2A NM_005911.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70
• Publications: 0 publications found

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]

PARTICL (HGNC:50886): (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005911.6. 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
	MAT2A	NM_005911.6	MANE Select	c.8G>A	p.Gly3Glu	missense	Exon 1 of 9	NP_005902.1	P31153-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	ENST00000306434.8	TSL:1 MANE Select	c.8G>A	p.Gly3Glu	missense	Exon 1 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000881374.1		c.8G>A	p.Gly3Glu	missense	Exon 1 of 9	ENSP00000551433.1
	MAT2A	ENST00000881376.1		c.8G>A	p.Gly3Glu	missense	Exon 1 of 9	ENSP00000551435.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.7	L
PhyloP100		8.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.82	P
Vest4		0.68
MutPred		0.33		Gain of solvent accessibility (P = 0.1045)
MVP		0.68
MPC		1.9
ClinPred		0.98	D
GERP RS		3.8
PromoterAI		0.14	Neutral
Varity_R		0.45
gMVP		0.87
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs1691387581; hg19: chr2-85766418;