21-46648497-A-G

Position:

• chr21-46648497-A-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.367A>G​(p.Thr123Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRMT2 NM_206962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15852797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4	c.367A>G	p.Thr123Ala	missense_variant	6/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8	c.367A>G	p.Thr123Ala	missense_variant	6/12	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

Nov 15, 2021

The c.367A>G (p.T123A) alteration is located in exon 6 (coding exon 4) of the PRMT2 gene. This alteration results from a A to G substitution at nucleotide position 367, causing the threonine (T) at amino acid position 123 to be replaced by an alanine (A). 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	0.065
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.62
DEOGEN2	Benign	0.28	T;.;.;T;.;T;.;T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.087	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.045	N;N;N;N;N;N;N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N;N;N;.
REVEL	Benign	0.099
Sift	Benign	0.51	T;T;T;T;T;T;T;T;T;.
Sift4G	Benign	0.75	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0050	B;.;.;B;.;B;.;.;.;.
Vest4		0.34
MutPred		0.25		Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);Loss of phosphorylation at T123 (P = 0.0169);.;
MVP		0.62
MPC		1.0
ClinPred		0.35	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.21

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: chr21-48068409;