21-46661860-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_206962.4(PRMT2):c.1021G>T(p.Ala341Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000066 in 1,364,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: PRMT2 NM_206962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40181077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.1021G>T	p.Ala341Ser	missense_variant	10/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.1021G>T	p.Ala341Ser	missense_variant	10/12	1	NM_206962.4	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000660 AC: 9 AN: 1364004 Hom.: 0 Cov.: 31 AF XY: 0.00000444 AC XY: 3 AN XY: 676428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.45e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ExAC AF: 0.0000166 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.1021G>T (p.A341S) alteration is located in exon 10 (coding exon 8) of the PRMT2 gene. This alteration results from a G to T substitution at nucleotide position 1021, causing the alanine (A) at amino acid position 341 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.76	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.49	T;T;T;T
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.69	P;P;P;.
Vest4		0.53
MutPred		0.42		Gain of MoRF binding (P = 0.1586);Gain of MoRF binding (P = 0.1586);Gain of MoRF binding (P = 0.1586);.;
MVP		0.65
MPC		1.0
ClinPred		0.48	T
GERP RS		5.3
Varity_R		0.15
gMVP		0.57

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: rs746391162; hg19: chr21-48081772;