rs1078004

Variant names:

• chr2-85542588-C-G
• rs1078004
• NM_005911.6:c.792C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-85542588-C-G
• chr2-85542588-C-A
• chr2-85542588-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005911.6(MAT2A):​c.792C>G​(p.Arg264Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,612,940 control chromosomes in the GnomAD database, including 176,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20992 hom., cov: 31)
  • Exomes 𝑓: 0.46 (155812 hom.)
• Consequence: MAT2A NM_005911.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.114
• Publications: 54 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]

MAT2A Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-85542588-C-G is Benign according to our data. Variant chr2-85542588-C-G is described in ClinVar as Benign. ClinVar VariationId is 381190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.114 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

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.792C>G	p.Arg264Arg	synonymous	Exon 7 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.792C>G	p.Arg264Arg	synonymous	Exon 7 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000409017.1	TSL:1	c.603C>G	p.Arg201Arg	synonymous	Exon 7 of 8	ENSP00000386353.1	P31153-2
	MAT2A	ENST00000481412.5	TSL:1	n.961C>G		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77923 AN: 151800 Hom.: 20955 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.507

GnomAD2 exomes AF: 0.442 AC: 111092 AN: 251118 AF XY: 0.442

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.383

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.459 AC: 670631 AN: 1461022 Hom.: 155812 Cov.: 42 AF XY: 0.457 AC XY: 332499 AN XY: 726854

African (AFR) AF: 0.692 AC: 23144 AN: 33456

American (AMR) AF: 0.341 AC: 15240 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10469 AN: 26124

East Asian (EAS) AF: 0.380 AC: 15064 AN: 39688

South Asian (SAS) AF: 0.393 AC: 33894 AN: 86208

European-Finnish (FIN) AF: 0.449 AC: 23963 AN: 53416

Middle Eastern (MID) AF: 0.439 AC: 2532 AN: 5762

European-Non Finnish (NFE) AF: 0.466 AC: 517893 AN: 1111350

Other (OTH) AF: 0.471 AC: 28432 AN: 60368

GnomAD4 genome AF: 0.514 AC: 78015 AN: 151918 Hom.: 20992 Cov.: 31 AF XY: 0.510 AC XY: 37837 AN XY: 74222

African (AFR) AF: 0.682 AC: 28247 AN: 41436

American (AMR) AF: 0.422 AC: 6436 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2015 AN: 5160

South Asian (SAS) AF: 0.393 AC: 1893 AN: 4818

European-Finnish (FIN) AF: 0.457 AC: 4822 AN: 10546

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31592 AN: 67924

Other (OTH) AF: 0.509 AC: 1070 AN: 2104

Alfa AF: 0.442 Hom.: 10736

Bravo AF: 0.517

EpiCase AF: 0.460

EpiControl AF: 0.465

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs1078004; hg19: chr2-85769711; COSMIC: COSV52087377; COSMIC: COSV52087377;