Variant chr12-50678822-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173602.3(DIP2B):c.1060T>C(p.Ser354Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00168 in 1,614,212 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 7 hom. )

Consequence

DIP2B
NM_173602.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.10

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009845793).

BP6

Variant 12-50678822-T-C is Benign according to our data. Variant chr12-50678822-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445445.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-50678822-T-C is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2B	NM_173602.3 link	c.1060T>C	p.Ser354Pro	missense_variant	8/38	ENST00000301180.10	NP_775873.2	Q9P265Q96IB4Q7Z3H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIP2B	ENST00000301180.10 link	c.1060T>C	p.Ser354Pro	missense_variant	8/38	5	NM_173602.3	ENSP00000301180.5	Q9P265
DIP2B	ENST00000546719.1 link	n.837T>C		non_coding_transcript_exon_variant	7/7	1
DIP2B	ENST00000549620.5 link	n.1216T>C		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000871

AC:

219

AN:

251424

Hom.:

AF XY:

0.000912

AC XY:

124

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00174

AC:

2545

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1266

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152332

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.000791

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jul 21, 2017

- -

DIP2B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.023

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.77

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

5.8

REVEL

Benign

0.073

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.35

MVP

0.043

MPC

0.44

ClinPred

0.0038

GERP RS

2.7

Varity_R

0.073

gMVP

0.71

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