rs41269807
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001393986.1(PRDM2):c.3070T>A(p.Ser1024Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0413 in 1,610,400 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 116 hom., cov: 30)
Exomes 𝑓: 0.042 ( 1431 hom. )
Consequence
PRDM2
NM_001393986.1 missense
NM_001393986.1 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 6.47
Genes affected
PRDM2 (HGNC:9347): (PR/SET domain 2) This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.00453192).
BP6
Variant 1-13780865-T-A is Benign according to our data. Variant chr1-13780865-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 403342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0312 (4710/150756) while in subpopulation NFE AF= 0.0467 (3166/67732). AF 95% confidence interval is 0.0454. There are 116 homozygotes in gnomad4. There are 2255 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 4710 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM2 | NM_001393986.1 | c.3070T>A | p.Ser1024Thr | missense_variant | 8/10 | ENST00000311066.10 | NP_001380915.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM2 | ENST00000311066.10 | c.3070T>A | p.Ser1024Thr | missense_variant | 8/10 | 5 | NM_001393986.1 | ENSP00000312352 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0313 AC: 4708AN: 150640Hom.: 116 Cov.: 30
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GnomAD3 exomes AF: 0.0346 AC: 8686AN: 251014Hom.: 184 AF XY: 0.0366 AC XY: 4962AN XY: 135622
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GnomAD4 exome AF: 0.0423 AC: 61765AN: 1459644Hom.: 1431 Cov.: 53 AF XY: 0.0421 AC XY: 30559AN XY: 726252
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GnomAD4 genome AF: 0.0312 AC: 4710AN: 150756Hom.: 116 Cov.: 30 AF XY: 0.0307 AC XY: 2255AN XY: 73570
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193
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155
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;.;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
P;P;.;.
Vest4
MPC
0.17
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at