2-85539298-A-G

Variant names:

• chr2-85539298-A-G
• rs756268499
• NM_005911.6:c.11A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005911.6(MAT2A):​c.11A>G​(p.Gln4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,604,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q4H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MAT2A NM_005911.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.58
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4106515).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

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.11A>G	p.Gln4Arg	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.11A>G	p.Gln4Arg	missense	Exon 1 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000881374.1		c.11A>G	p.Gln4Arg	missense	Exon 1 of 9	ENSP00000551433.1
	MAT2A	ENST00000881376.1		c.11A>G	p.Gln4Arg	missense	Exon 1 of 9	ENSP00000551435.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1451978 Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9 AN XY: 722462

African (AFR) AF: 0.00 AC: 0 AN: 32184

American (AMR) AF: 0.00 AC: 0 AN: 43676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.00 AC: 0 AN: 38304

South Asian (SAS) AF: 0.00 AC: 0 AN: 85066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000181 AC: 20 AN: 1108026

Other (OTH) AF: 0.00 AC: 0 AN: 59898

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.024
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.4	L
PhyloP100		2.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.15	N
REVEL	Uncertain	0.46
Sift	Benign	0.56	T
Sift4G	Benign	0.55	T
Polyphen		0.036	B
Vest4		0.47
MutPred		0.23		Gain of methylation at Q4 (P = 0.0074)
MVP		0.89
MPC		1.3
ClinPred		0.64	D
GERP RS		4.7
PromoterAI		0.080	Neutral
Varity_R		0.22
gMVP		0.73
Mutation Taster		=81/19	polymorphism

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: rs756268499; hg19: chr2-85766421;