21-46649728-A-C

Position:

• chr21-46649728-A-C

Variant summary

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

The NM_206962.4(PRMT2):​c.643A>C​(p.Thr215Pro) 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: 4.96

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]

PRMT2 (HGNC:):

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	Protein	UniProt
PRMT2	NM_206962.4	c.643A>C	p.Thr215Pro	missense_variant	7/12	ENST00000355680.8	NP_996845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT2	ENST00000355680.8	c.643A>C	p.Thr215Pro	missense_variant	7/12	1	NM_206962.4	ENSP00000347906.3

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

May 14, 2024

The c.643A>C (p.T215P) alteration is located in exon 7 (coding exon 5) of the PRMT2 gene. This alteration results from a A to C substitution at nucleotide position 643, causing the threonine (T) at amino acid position 215 to be replaced by a proline (P). 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	0.76
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;.;.;D;.;D;.;T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	.;D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;L;L;L;L;L;L;.;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D;D;D;D;D;.
REVEL	Benign	0.23
Sift	Uncertain	0.017	D;D;D;D;T;D;D;T;T;.
Sift4G	Benign	0.17	T;D;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;.;D;.;D;.;.;.;.
Vest4		0.75
MutPred		0.55		Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);Gain of catalytic residue at T215 (P = 0.3293);.;
MVP		0.41
MPC		0.77
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.55
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr21-48069640;