dbSNP rs3743123: GJD2:p.Ser196Ser (chr15-34752856-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020660.3(GJD2):c.588C>T(p.Ser196Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,800 control chromosomes in the GnomAD database, including 81,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7331 hom., cov: 31)

Exomes 𝑓: 0.32 ( 74231 hom. )

Consequence

GJD2
NM_020660.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

28 publications found

Variant links:

Genes affected

GJD2 (HGNC:19154): (gap junction protein delta 2) This gene encodes a member of the connexin protein family. Connexins are gap junction proteins which are arranged in groups of 6 around a central pore to form a connexon, a component of the gap junction intercellular channel. The channels formed by this protein allow cationic molecule exchange between human beta cells and may function in the regulation of insulin secretion. [provided by RefSeq, Oct 2012]

GJD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=0.597 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD2	NM_020660.3 link	c.588C>T	p.Ser196Ser	synonymous_variant	Exon 2 of 2	ENST00000290374.5	NP_065711.1	Q9UKL4
GJD2	XM_017022438.2 link	c.435C>T	p.Ser145Ser	synonymous_variant	Exon 2 of 2		XP_016877927.1	A0A654IE23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJD2	ENST00000290374.5 link	c.588C>T	p.Ser196Ser	synonymous_variant	Exon 2 of 2	1	NM_020660.3	ENSP00000290374.4		Q9UKL4

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46916

AN:

151910

Hom.:

7332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.323

AC:

81127

AN:

251476

AF XY:

0.326

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.316

AC:

462304

AN:

1461772

Hom.:

74231

Cov.:

AF XY:

0.319

AC XY:

232027

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.291

AC:

9754

AN:

33480

American (AMR)

AF:

0.360

AC:

16097

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

8823

AN:

26134

East Asian (EAS)

AF:

0.330

AC:

13104

AN:

39700

South Asian (SAS)

AF:

0.418

AC:

36086

AN:

86254

European-Finnish (FIN)

AF:

0.278

AC:

14840

AN:

53418

Middle Eastern (MID)

AF:

0.370

AC:

2135

AN:

5766

European-Non Finnish (NFE)

AF:

0.308

AC:

342239

AN:

1111902

Other (OTH)

AF:

0.318

AC:

19226

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19675

39351

59026

78702

98377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11348

22696

34044

45392

56740

<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:

0.309

AC:

46938

AN:

152028

Hom.:

7331

Cov.:

AF XY:

0.309

AC XY:

22981

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.299

AC:

12384

AN:

41464

American (AMR)

AF:

0.331

AC:

5063

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1173

AN:

3468

East Asian (EAS)

AF:

0.267

AC:

1374

AN:

5154

South Asian (SAS)

AF:

0.420

AC:

2016

AN:

4804

European-Finnish (FIN)

AF:

0.288

AC:

3043

AN:

10556

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20786

AN:

67972

Other (OTH)

AF:

0.335

AC:

706

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1651

3303

4954

6606

8257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.312

Hom.:

6383

Bravo

AF:

0.309

Asia WGS

AF:

0.371

AC:

1288

AN:

3478

EpiCase

AF:

0.316

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.9

(source)

DANN

Benign

0.81

PhyloP100

0.60

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over