chr12-50546024-A-T

Variant names:

• chr12-50546024-A-T
• rs7487429
• NM_173602.3:c.100+40784A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173602.3(DIP2B):​c.100+40784A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,156 control chromosomes in the GnomAD database, including 7,950 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 0.32 (7950 hom., cov: 32)
• Consequence: DIP2B NM_173602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 10 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2B	NM_173602.3	c.100+40784A>T		intron_variant	Intron 1 of 37	ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10	c.100+40784A>T		intron_variant	Intron 1 of 37	5	NM_173602.3	ENSP00000301180.5
DIP2B	ENST00000549620.5	n.256+40784A>T		intron_variant	Intron 1 of 7	1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48598 AN: 152038 Hom.: 7955 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48611 AN: 152156 Hom.: 7950 Cov.: 32 AF XY: 0.316 AC XY: 23493 AN XY: 74392

African (AFR) AF: 0.321 AC: 13310 AN: 41506

American (AMR) AF: 0.266 AC: 4065 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1269 AN: 5178

South Asian (SAS) AF: 0.389 AC: 1878 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2787 AN: 10582

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23235 AN: 67992

Other (OTH) AF: 0.346 AC: 731 AN: 2114

Alfa AF: 0.166 Hom.: 307

Bravo AF: 0.321

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7487429; hg19: chr12-50939807;