21-46649698-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206962.4(PRMT2):c.613G>A(p.Val205Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.23

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.613G>A	p.Val205Met	missense_variant	7/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.613G>A	p.Val205Met	missense_variant	7/12	1	NM_206962.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 17, 2021

The c.613G>A (p.V205M) alteration is located in exon 7 (coding exon 5) of the PRMT2 gene. This alteration results from a G to A substitution at nucleotide position 613, causing the valine (V) at amino acid position 205 to be replaced by a methionine (M). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
Cadd	Pathogenic	30
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;.;.;D;.;D;.;T;.;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.75	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.9	H;H;H;H;H;H;H;.;H;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D;D;D;D;D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;D;D;D;D;D;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;D;.;D;.;.;.;.
Vest4		0.78
MutPred		0.70		Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);Gain of catalytic residue at V205 (P = 0.0155);.;
MVP		0.62
MPC		1.5
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-48069610;