chr1-13780865-T-A

Position:

chr1-13780865-T-A

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.47

Variant links:

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]

PRDM2 links:

Genome browser will be placed here

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 linkuse as main transcript	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 linkuse as main transcript	c.3070T>A	p.Ser1024Thr	missense_variant	8/10	5	NM_001393986.1	ENSP00000312352	P1	Q13029-1

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4708

AN:

150640

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.000588

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.0468

Gnomad OTH

AF:

0.0336

GnomAD3 exomes

AF:

0.0346

AC:

8686

AN:

251014

Hom.:

184

AF XY:

0.0366

AC XY:

4962

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.00744

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0461

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0381

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.0470

Gnomad OTH exome

AF:

0.0403

GnomAD4 exome

AF:

0.0423

AC:

61765

AN:

1459644

Hom.:

1431

Cov.:

AF XY:

0.0421

AC XY:

30559

AN XY:

726252

show subpopulations

Gnomad4 AFR exome

AF:

0.00703

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0394

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0466

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0312

AC:

4710

AN:

150756

Hom.:

116

Cov.:

AF XY:

0.0307

AC XY:

2255

AN XY:

73570

show subpopulations

Gnomad4 AFR

AF:

0.00845

Gnomad4 AMR

AF:

0.0348

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.000590

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0332

Alfa

AF:

0.0434

Hom.:

127

Bravo

AF:

0.0303

TwinsUK

AF:

0.0520

AC:

193

ALSPAC

AF:

0.0402

AC:

155

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.0451

AC:

388

ExAC

AF:

0.0351

AC:

4258

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0486

EpiControl

AF:

0.0470

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.084

.;T;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;D;.;T

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.4

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.87

N;N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.089

T;T;T;T

Polyphen

0.86

P;P;.;.

Vest4

0.24

MPC

0.17

ClinPred

0.033

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over