dbSNP rs61927768: DIP2B:c.-196G>A (chr12-50504945-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173602.3(DIP2B):c.-196G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 533,844 control chromosomes in the GnomAD database, including 31,510 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 0.20 ( 3824 hom., cov: 32)

Exomes 𝑓: 0.30 ( 27686 hom. )

Consequence

DIP2B
NM_173602.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

13 publications found

Variant links:

COSMIC-nc: COSV56594422

Genes affected

DIP2B (HGNC:29284): (disco interacting protein 2 homolog B) This gene encodes a member of the disco-interacting protein homolog 2 protein family. The encoded protein contains a binding site for the transcriptional regulator DNA methyltransferase 1 associated protein 1 as well as AMP-binding sites. The presence of these sites suggests that the encoded protein may participate in DNA methylation. This gene is located near a folate-sensitive fragile site, and CGG-repeat expansion in the promoter of this gene which affects transcription has been detected in individuals containing this fragile site on chromosome 12. [provided by RefSeq, Aug 2011]

DIP2B Gene-Disease associations (from GenCC):

intellectual disability, FRA12A type
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

DIP2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2B	NM_173602.3 link	c.-196G>A		upstream_gene_variant		ENST00000301180.10	NP_775873.2	Q9P265Q96IB4Q7Z3H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10 link	c.-196G>A		upstream_gene_variant		5	NM_173602.3	ENSP00000301180.5		Q9P265
DIP2B	ENST00000549620.5 link	n.-40G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

29843

AN:

149824

Hom.:

3824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.0611

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.211

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.301

AC:

115416

AN:

383896

Hom.:

27686

Cov.:

AF XY:

0.300

AC XY:

62368

AN XY:

207948

show subpopulations

African (AFR)

AF:

0.0608

AC:

499

AN:

8202

American (AMR)

AF:

0.174

AC:

2508

AN:

14378

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

2406

AN:

10210

East Asian (EAS)

AF:

0.0692

AC:

1824

AN:

26352

South Asian (SAS)

AF:

0.279

AC:

12144

AN:

43490

European-Finnish (FIN)

AF:

0.295

AC:

7640

AN:

25894

Middle Eastern (MID)

AF:

0.294

AC:

479

AN:

1632

European-Non Finnish (NFE)

AF:

0.352

AC:

81467

AN:

231652

Other (OTH)

AF:

0.292

AC:

6449

AN:

22086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

2899

5797

8696

11594

14493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.199

AC:

29837

AN:

149948

Hom.:

3824

Cov.:

AF XY:

0.195

AC XY:

14292

AN XY:

73224

show subpopulations

African (AFR)

AF:

0.0560

AC:

2307

AN:

41200

American (AMR)

AF:

0.166

AC:

2499

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

591

AN:

3380

East Asian (EAS)

AF:

0.0610

AC:

315

AN:

5164

South Asian (SAS)

AF:

0.242

AC:

1152

AN:

4758

European-Finnish (FIN)

AF:

0.240

AC:

2474

AN:

10292

Middle Eastern (MID)

AF:

0.221

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.296

AC:

19811

AN:

66902

Other (OTH)

AF:

0.224

AC:

465

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

1151

2302

3454

4605

5756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.127

Hom.:

247

Bravo

AF:

0.184

Asia WGS

AF:

0.155

AC:

538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.7

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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