1-13731083-G-T

Variant names:

• chr1-13731083-G-T
• NM_001393986.1:c.93G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393986.1(PRDM2):​c.93G>T​(p.Arg31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM2	NM_001393986.1	c.93G>T	p.Arg31Ser	missense_variant	Exon 3 of 10	ENST00000311066.10	NP_001380915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM2	ENST00000311066.10	c.93G>T	p.Arg31Ser	missense_variant	Exon 3 of 10	5	NM_001393986.1	ENSP00000312352.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461004 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	.;.;.;T
Eigen	Benign	-0.070
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.56	.;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.66, 0.53	.;.;P;P
Vest4		0.55, 0.80, 0.83
MutPred		0.48		Loss of MoRF binding (P = 0.0322);Loss of MoRF binding (P = 0.0322);Loss of MoRF binding (P = 0.0322);Loss of MoRF binding (P = 0.0322);
MVP		0.74
MPC		0.79
ClinPred		0.85	D
GERP RS		3.9
Varity_R		0.39
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.36		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-14057578;