chr1-13778727-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001393986.1(PRDM2):c.932G>A(p.Arg311Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,614,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
PRDM2
NM_001393986.1 missense
NM_001393986.1 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.285
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.022797108).
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM2 | NM_001393986.1 | c.932G>A | p.Arg311Gln | missense_variant | 8/10 | ENST00000311066.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM2 | ENST00000311066.10 | c.932G>A | p.Arg311Gln | missense_variant | 8/10 | 5 | NM_001393986.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152116Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000191 AC: 48AN: 251398Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135872
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GnomAD4 exome AF: 0.000213 AC: 312AN: 1461888Hom.: 0 Cov.: 58 AF XY: 0.000230 AC XY: 167AN XY: 727244
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152234Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74464
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2022 | The c.932G>A (p.R311Q) alteration is located in exon 8 (coding exon 7) of the PRDM2 gene. This alteration results from a G to A substitution at nucleotide position 932, causing the arginine (R) at amino acid position 311 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;P;.;.
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
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