rs11543052

Variant names:

• chr21-46636464-T-C
• rs11543052
• NM_206962.4:c.-140T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_206962.4(PRMT2):​c.-140T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 154,982 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: PRMT2 NM_206962.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT2	NM_206962.4	c.-140T>C		5_prime_UTR_variant	Exon 2 of 12	ENST00000355680.8	NP_996845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRMT2	ENST00000355680.8	c.-140T>C		5_prime_UTR_variant	Exon 2 of 12	1	NM_206962.4	ENSP00000347906.3

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1622 AN: 152216 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0113 AC: 30 AN: 2648 Hom.: 1 Cov.: 0 AF XY: 0.0109 AC XY: 15 AN XY: 1376

African (AFR) AF: 0.00 AC: 0 AN: 68

American (AMR) AF: 0.00 AC: 0 AN: 112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 68

East Asian (EAS) AF: 0.00 AC: 0 AN: 34

South Asian (SAS) AF: 0.00309 AC: 1 AN: 324

European-Finnish (FIN) AF: 0.0319 AC: 3 AN: 94

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.0139 AC: 25 AN: 1800

Other (OTH) AF: 0.00704 AC: 1 AN: 142

GnomAD4 genome AF: 0.0106 AC: 1621 AN: 152334 Hom.: 10 Cov.: 33 AF XY: 0.0112 AC XY: 831 AN XY: 74484

African (AFR) AF: 0.00265 AC: 110 AN: 41572

American (AMR) AF: 0.00804 AC: 123 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00310 AC: 15 AN: 4832

European-Finnish (FIN) AF: 0.0320 AC: 339 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0143 AC: 974 AN: 68030

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.0119 Hom.: 20

Bravo AF: 0.00834

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs11543052; hg19: chr21-48056376;