Variant 12-50671224-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_173602.3(DIP2B):c.466C>T(p.Arg156Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DIP2B
NM_173602.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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:

DIP2B (HGNC:):

DIP2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DIP2B. . Gene score misZ 3.1809 (greater than the threshold 3.09). Trascript score misZ 4.0584 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, FRA12A type.

BS2

High AC in GnomAdExome4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2B	NM_173602.3 linkuse as main transcript	c.466C>T	p.Arg156Cys	missense_variant	5/38	ENST00000301180.10	NP_775873.2	Q9P265Q96IB4Q7Z3H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIP2B	ENST00000301180.10 linkuse as main transcript	c.466C>T	p.Arg156Cys	missense_variant	5/38	5	NM_173602.3	ENSP00000301180.5	Q9P265
DIP2B	ENST00000546719.1 linkuse as main transcript	n.243C>T		non_coding_transcript_exon_variant	4/7	1
DIP2B	ENST00000549620.5 linkuse as main transcript	n.622C>T		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251394

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135862

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.466C>T (p.R156C) alteration is located in exon 5 (coding exon 5) of the DIP2B gene. This alteration results from a C to T substitution at nucleotide position 466, causing the arginine (R) at amino acid position 156 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.19

Sift

Uncertain

0.011

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.82

MVP

0.082

MPC

1.1

ClinPred

0.90

GERP RS

4.4

Varity_R

0.36

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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