rs2839377

Positions:

• chr21-46657900-C-T
• chr21-46657900-C-G

Variant summary

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

The NM_206962.4(PRMT2):​c.655-845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,116 control chromosomes in the GnomAD database, including 18,854 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 0.49 (18854 hom., cov: 34)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PRMT2 NM_206962.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

Genes affected

PRMT2 (HGNC:5186): (protein arginine methyltransferase 2) Enables several functions, including nuclear receptor binding activity; peroxisome proliferator activated receptor binding activity; and protein homodimerization activity. Involved in several processes, including histone methylation; regulation of androgen receptor signaling pathway; and regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRMT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT2	NM_206962.4	c.655-845C>T		intron_variant		ENST00000355680.8	NP_996845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT2	ENST00000355680.8	c.655-845C>T		intron_variant		1	NM_206962.4	ENSP00000347906.3

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74741 AN: 151996 Hom.: 18852 Cov.: 34

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.492 AC: 74774 AN: 152114 Hom.: 18854 Cov.: 34 AF XY: 0.499 AC XY: 37082 AN XY: 74352

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.526

Alfa AF: 0.530 Hom.: 36111

Bravo AF: 0.479

Asia WGS AF: 0.570 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.69
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: rs2839377; hg19: chr21-48077812;