Genetic Variant JDP2:p.Met1? (chr14-75437922-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PVS1_SupportingBS2

The NM_001135048.2(JDP2):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,605,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

JDP2
NM_001135048.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Publications

1 publications found

Variant links:

Genes affected

JDP2 (HGNC:17546): (Jun dimerization protein 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

JDP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 2 codons. Genomic position: 75437924. Lost 0.008 part of the original CDS.

BS2

High AC in GnomAdExome4 at 70 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135048.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JDP2	NM_001135048.2	MANE Select	c.2T>C	p.Met1?	start_lost	Exon 2 of 4	NP_001128520.1	Q8WYK2-1
JDP2	NM_001135047.2		c.2T>C	p.Met1?	start_lost	Exon 2 of 4	NP_001128519.1	Q8WYK2-1
JDP2	NM_130469.3		c.2T>C	p.Met1?	start_lost	Exon 2 of 4	NP_569736.1	Q8WYK2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JDP2	ENST00000651602.1	MANE Select	c.2T>C	p.Met1?	start_lost	Exon 2 of 4	ENSP00000498745.1	Q8WYK2-1
JDP2	ENST00000435893.6	TSL:1	c.2T>C	p.Met1?	start_lost	Exon 2 of 4	ENSP00000399587.2	Q8WYK2-1
JDP2	ENST00000267569.5	TSL:1	c.35T>C	p.Met12Thr	missense	Exon 2 of 4	ENSP00000267569.5	Q8WYK2-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000208

AC:

AN:

240018

AF XY:

0.0000231

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000462

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000482

AC:

AN:

1453356

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

721866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33308

American (AMR)

AF:

0.00

AC:

AN:

44042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.00

AC:

AN:

85224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5128

European-Non Finnish (NFE)

AF:

0.0000623

AC:

AN:

1107594

Other (OTH)

AF:

0.0000167

AC:

AN:

59946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41480

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

Eigen

Benign

-0.030

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.98

PhyloP100

2.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.40

MVP

0.24

MPC

0.62

ClinPred

0.96

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.74

gMVP

0.77

Mutation Taster

=69/31

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over