2-207608460-G-A

Position:

• chr2-207608460-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000458426.5(METTL21A):​c.259+13346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,636 control chromosomes in the GnomAD database, including 4,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4566 hom., cov: 31)
• Consequence: METTL21A ENST00000458426.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

Genes affected

METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL21A	NM_001308021.3	c.259+13346C>T		intron_variant			NP_001294950.1
METTL21A	NM_001330131.2	c.259+13346C>T		intron_variant			NP_001317060.1
METTL21A	NM_001330132.3	c.259+13346C>T		intron_variant			NP_001317061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL21A	ENST00000458426.5	c.259+13346C>T		intron_variant		1		ENSP00000389684
METTL21A	ENST00000425132.5	c.259+13346C>T		intron_variant		2		ENSP00000400730
METTL21A	ENST00000432416.5	c.259+13346C>T		intron_variant		3		ENSP00000416570

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32965 AN: 151518 Hom.: 4565 Cov.: 31

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 32970 AN: 151636 Hom.: 4566 Cov.: 31 AF XY: 0.215 AC XY: 15940 AN XY: 74046

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.194

Alfa AF: 0.240 Hom.: 827

Bravo AF: 0.213

Asia WGS AF: 0.206 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7569963; hg19: chr2-208473184;