chr1-13780865-T-C

Variant names:

• chr1-13780865-T-C
• rs41269807
• NM_001393986.1:c.3070T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393986.1(PRDM2):​c.3070T>C​(p.Ser1024Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S1024T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47
• Publications: 9 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20476258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393986.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	NM_001393986.1	MANE Select	c.3070T>C	p.Ser1024Pro	missense	Exon 8 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.3070T>C	p.Ser1024Pro	missense	Exon 8 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.3070T>C	p.Ser1024Pro	missense	Exon 8 of 9	NP_056950.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.3070T>C	p.Ser1024Pro	missense	Exon 8 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.3070T>C	p.Ser1024Pro	missense	Exon 8 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000343137.8	TSL:1	c.2467T>C	p.Ser823Pro	missense	Exon 4 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.024	D
Polyphen		0.34	B
Vest4		0.58
MutPred		0.26		Gain of catalytic residue at S1024 (P = 9e-04)
MVP		0.068
MPC		0.24
ClinPred		0.69	D
GERP RS		6.0
Varity_R		0.42
gMVP		0.50
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs41269807; hg19: chr1-14107360;