Variant 21-46661935-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_206962.4(PRMT2):c.1096C>A(p.Pro366Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000152 in 1,294,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

PRMT2
NM_206962.4 missense, splice_region

Scores

Splicing: ADA: 0.9455

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.16

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01884982).

BP6

Variant 21-46661935-C-A is Benign according to our data. Variant chr21-46661935-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 764005.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT2	NM_206962.4 linkuse as main transcript	c.1096C>A	p.Pro366Thr	missense_variant, splice_region_variant	10/12	ENST00000355680.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT2	ENST00000355680.8 linkuse as main transcript	c.1096C>A	p.Pro366Thr	missense_variant, splice_region_variant	10/12	1	NM_206962.4	P1	P55345-1

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

141274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000718

Gnomad ASJ

AF:

0.00685

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000774

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

98922

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

56882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000342

Gnomad ASJ exome

AF:

0.00445

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

168

AN:

1153316

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

561484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000346

Gnomad4 ASJ exome

AF:

0.00677

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000320

Gnomad4 OTH exome

AF:

0.000585

GnomAD4 genome

AF:

0.000205

AC:

AN:

141372

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

68340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000717

Gnomad4 ASJ

AF:

0.00685

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000775

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000613

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000145

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;D;D;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.90

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.98

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;N

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.091

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.99

D;D;D;.

Vest4

0.56

MVP

0.47

MPC

1.6

ClinPred

0.13

GERP RS

5.3

Varity_R

0.28

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over