chr21-46657900-C-T

Variant names:

• chr21-46657900-C-T
• rs2839377
• NM_206962.4:c.655-845C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001535.5(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_001535.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001535.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT2	NM_206962.4	MANE Select	c.655-845C>T		intron	N/A	NP_996845.1
	PRMT2	NM_001535.5		c.655-845C>T		intron	N/A	NP_001526.2
	PRMT2	NM_001242864.3		c.655-3900C>T		intron	N/A	NP_001229793.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT2	ENST00000355680.8	TSL:1 MANE Select	c.655-845C>T		intron	N/A	ENSP00000347906.3
	PRMT2	ENST00000397638.7	TSL:1	c.655-845C>T		intron	N/A	ENSP00000380760.2
	PRMT2	ENST00000440086.5	TSL:1	c.655-3900C>T		intron	N/A	ENSP00000397266.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.357 AC: 14821 AN: 41476

American (AMR) AF: 0.515 AC: 7879 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2055 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2938 AN: 5176

South Asian (SAS) AF: 0.619 AC: 2989 AN: 4830

European-Finnish (FIN) AF: 0.575 AC: 6073 AN: 10564

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36167 AN: 67980

Other (OTH) AF: 0.526 AC: 1112 AN: 2114

Alfa AF: 0.518 Hom.: 56360

Bravo AF: 0.479

Asia WGS AF: 0.570 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2839377; hg19: chr21-48077812;