21-46644495-C-T

Position:

• chr21-46644495-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_206962.4(PRMT2):​c.327+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,568,184 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (82 hom.)
• Consequence: PRMT2 NM_206962.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008422
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0400

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

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-46644495-C-T is Benign according to our data. Variant chr21-46644495-C-T is described in ClinVar as [Benign]. Clinvar id is 710386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT2	NM_206962.4	c.327+7C>T		splice_region_variant, intron_variant		ENST00000355680.8	NP_996845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT2	ENST00000355680.8	c.327+7C>T		splice_region_variant, intron_variant		1	NM_206962.4	ENSP00000347906.3

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 787 AN: 152090 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00499 AC: 1060 AN: 212408 Hom.: 5 AF XY: 0.00525 AC XY: 608 AN XY: 115784

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00179

Gnomad NFE exome AF: 0.00938

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00900 AC: 12737 AN: 1415976 Hom.: 82 Cov.: 31 AF XY: 0.00870 AC XY: 6103 AN XY: 701390

Gnomad4 AFR exome AF: 0.00113

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.0000823

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000501

Gnomad4 FIN exome AF: 0.00232

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00557

GnomAD4 genome AF: 0.00517 AC: 787 AN: 152208 Hom.: 1 Cov.: 32 AF XY: 0.00458 AC XY: 341 AN XY: 74416

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00950

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00679 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.010
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: rs116875508; hg19: chr21-48064407;