21-46643596-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206962.4(PRMT2):c.101A>T(p.Glu34Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRMT2 NM_206962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.101A>T	p.Glu34Val	missense_variant	4/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.101A>T	p.Glu34Val	missense_variant	4/12	1	NM_206962.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 30, 2023

The c.101A>T (p.E34V) alteration is located in exon 4 (coding exon 2) of the PRMT2 gene. This alteration results from a A to T substitution at nucleotide position 101, causing the glutamic acid (E) at amino acid position 34 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;.;T;.;T;.;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.32	N;N;N;N;N;N;N;.;N
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.012	D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.81	T;T;T;T;T;T;T;T;T
Polyphen		0.94	P;.;.;P;.;P;.;.;.
Vest4		0.60
MutPred		0.46		Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);Loss of disorder (P = 0.0295);
MVP		0.55
MPC		1.7
ClinPred		0.73	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs373570744; hg19: chr21-48063508;