chr1-13780865-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 4710 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM2	NM_001393986.1 link	c.3070T>A	p.Ser1024Thr	missense_variant	Exon 8 of 10	ENST00000311066.10	NP_001380915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM2	ENST00000311066.10 link	c.3070T>A	p.Ser1024Thr	missense_variant	Exon 8 of 10	5	NM_001393986.1	ENSP00000312352.6		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

GnomAD2 exomes

AF:

0.0346

AC:

8686

AN:

251014

AF XY:

0.0366

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 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

African (AFR)

AF:

0.00703

AC:

235

AN:

33438

American (AMR)

AF:

0.0232

AC:

1038

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

1163

AN:

26110

East Asian (EAS)

AF:

0.000101

AC:

AN:

39692

South Asian (SAS)

AF:

0.0394

AC:

3397

AN:

86164

European-Finnish (FIN)

AF:

0.0274

AC:

1466

AN:

53412

Middle Eastern (MID)

AF:

0.0475

AC:

274

AN:

5764

European-Non Finnish (NFE)

AF:

0.0466

AC:

51783

AN:

1110076

Other (OTH)

AF:

0.0399

AC:

2405

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3573

7146

10720

14293

17866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1912

3824

5736

7648

9560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0312

AC:

4710

AN:

150756

Hom.:

116

Cov.:

AF XY:

0.0307

AC XY:

2255

AN XY:

73570

show subpopulations

African (AFR)

AF:

0.00845

AC:

346

AN:

40956

American (AMR)

AF:

0.0348

AC:

527

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.0470

AC:

163

AN:

3466

East Asian (EAS)

AF:

0.000590

AC:

AN:

5086

South Asian (SAS)

AF:

0.0365

AC:

172

AN:

4712

European-Finnish (FIN)

AF:

0.0241

AC:

250

AN:

10352

Middle Eastern (MID)

AF:

0.0276

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0467

AC:

3166

AN:

67732

Other (OTH)

AF:

0.0332

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

206

412

617

823

1029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.;.

PhyloP100

6.5

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

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over