chr1-13742153-T-C

Variant names:

• chr1-13742153-T-C
• NM_001393986.1:c.380T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001393986.1(PRDM2):​c.380T>C​(p.Leu127Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.21
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919

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.380T>C	p.Leu127Ser	missense	Exon 5 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.380T>C	p.Leu127Ser	missense	Exon 5 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.380T>C	p.Leu127Ser	missense	Exon 5 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.380T>C	p.Leu127Ser	missense	Exon 5 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.380T>C	p.Leu127Ser	missense	Exon 5 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000376048.9	TSL:2	c.380T>C	p.Leu127Ser	missense	Exon 5 of 8	ENSP00000365216.5	Q13029-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.0025	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.011	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.91
MutPred		0.82		Loss of catalytic residue at L127 (P = 0.0017)
MVP		0.86
MPC		0.89
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.58
gMVP		0.82
Mutation Taster		=13/87	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

hg19: chr1-14068648;