21-46661896-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_206962.4(PRMT2):c.1057G>A(p.Gly353Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,487,760 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 26)
  • Exomes 𝑓: 0.0040 (25 hom.)
• Consequence: PRMT2 NM_206962.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.85

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004463196).
• BP6: Variant 21-46661896-G-A is Benign according to our data. Variant chr21-46661896-G-A is described in ClinVar as [Benign]. Clinvar id is 718694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.1057G>A	p.Gly353Arg	missense_variant	10/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.1057G>A	p.Gly353Arg	missense_variant	10/12	1	NM_206962.4	P1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 546 AN: 148842 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.000771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000869

Gnomad ASJ AF: 0.00464

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000427

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00401 AC: 676 AN: 168482 Hom.: 6 AF XY: 0.00390 AC XY: 372 AN XY: 95412

Gnomad AFR exome AF: 0.000561

Gnomad AMR exome AF: 0.000864

Gnomad ASJ exome AF: 0.00483

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000911

Gnomad FIN exome AF: 0.0190

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00403 AC: 5394 AN: 1338810 Hom.: 25 Cov.: 32 AF XY: 0.00392 AC XY: 2601 AN XY: 662684

Gnomad4 AFR exome AF: 0.000457

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00440

Gnomad4 EAS exome AF: 0.0000307

Gnomad4 SAS exome AF: 0.000848

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.00392

Gnomad4 OTH exome AF: 0.00350

GnomAD4 genome AF: 0.00366 AC: 545 AN: 148950 Hom.: 2 Cov.: 26 AF XY: 0.00386 AC XY: 280 AN XY: 72632

Gnomad4 AFR AF: 0.000768

Gnomad4 AMR AF: 0.000868

Gnomad4 ASJ AF: 0.00464

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000428

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.00412

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00331 Hom.: 1

Bravo AF: 0.00232

ESP6500AA AF: 0.000235 AC: 1

ESP6500EA AF: 0.00203 AC: 17

ExAC AF: 0.00297 AC: 347

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Benign	0.066
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
MetaRNN	Benign	0.0045	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.052	B;B;B;.
Vest4		0.11
MutPred		0.26		Loss of catalytic residue at E352 (P = 0.1736);Loss of catalytic residue at E352 (P = 0.1736);Loss of catalytic residue at E352 (P = 0.1736);.;
MVP		0.23
MPC		1.2
ClinPred		0.020	T
GERP RS		5.3
Varity_R		0.095
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs142055128; hg19: chr21-48081808; COSMIC: COSV99053381; COSMIC: COSV99053381;