21-46661845-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206962.4(PRMT2):c.1006C>G(p.Leu336Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,363,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PRMT2 NM_206962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17972589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.1006C>G	p.Leu336Val	missense_variant	10/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.1006C>G	p.Leu336Val	missense_variant	10/12	1	NM_206962.4	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1363224 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 675762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

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 31, 2022

The c.1006C>G (p.L336V) alteration is located in exon 10 (coding exon 8) of the PRMT2 gene. This alteration results from a C to G substitution at nucleotide position 1006, causing the leucine (L) at amino acid position 336 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	0.17
BayesDel_addAF	Benign	0.00036	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.078	N
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.66	N;N;N;.
MutationTaster	Benign	1.0	D;D;D;N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.93	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.72	P;P;P;.
Vest4		0.35
MutPred		0.46		Gain of MoRF binding (P = 0.1234);Gain of MoRF binding (P = 0.1234);Gain of MoRF binding (P = 0.1234);.;
MVP		0.50
MPC		0.62
ClinPred		0.62	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.15
gMVP		0.33

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: chr21-48081757;