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GeneBe

21-46649691-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_206962.4(PRMT2):c.606C>T(p.Pro202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,802 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 66 hom. )

Consequence

PRMT2
NM_206962.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-46649691-C-T is Benign according to our data. Variant chr21-46649691-C-T is described in ClinVar as [Benign]. Clinvar id is 779049.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.24 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00268 (407/152134) while in subpopulation AMR AF= 0.022 (336/15284). AF 95% confidence interval is 0.02. There are 5 homozygotes in gnomad4. There are 212 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRMT2NM_206962.4 linkuse as main transcriptc.606C>T p.Pro202= synonymous_variant 7/12 ENST00000355680.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRMT2ENST00000355680.8 linkuse as main transcriptc.606C>T p.Pro202= synonymous_variant 7/121 NM_206962.4 P1P55345-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00264
AC:
401
AN:
152016
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00131
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0216
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.000580
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00770
AC:
1930
AN:
250750
Hom.:
57
AF XY:
0.00575
AC XY:
781
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.0532
Gnomad ASJ exome
AF:
0.000995
Gnomad EAS exome
AF:
0.000926
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00408
GnomAD4 exome
AF:
0.00164
AC:
2403
AN:
1461668
Hom.:
66
Cov.:
31
AF XY:
0.00138
AC XY:
1006
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00108
Gnomad4 AMR exome
AF:
0.0480
Gnomad4 ASJ exome
AF:
0.00107
Gnomad4 EAS exome
AF:
0.00154
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.00121
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00268
AC:
407
AN:
152134
Hom.:
5
Cov.:
33
AF XY:
0.00285
AC XY:
212
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00130
Gnomad4 AMR
AF:
0.0220
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.000582
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.000610
Hom.:
0
Bravo
AF:
0.00529
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
2.2
Dann
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs148075005; hg19: chr21-48069603; API