chr12-50649107-C-A

Position:

• chr12-50649107-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173602.3(DIP2B):​c.301+8255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,904 control chromosomes in the GnomAD database, including 7,938 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 (7938 hom., cov: 32)
• Consequence: DIP2B NM_173602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIP2B	NM_173602.3	c.301+8255C>A		intron_variant		ENST00000301180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIP2B	ENST00000301180.10	c.301+8255C>A		intron_variant		5	NM_173602.3	P1
DIP2B	ENST00000546719.1	n.49-5904C>A		intron_variant, non_coding_transcript_variant		1
DIP2B	ENST00000549620.5	n.457+8255C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48540 AN: 151786 Hom.: 7943 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.320 AC: 48553 AN: 151904 Hom.: 7938 Cov.: 32 AF XY: 0.316 AC XY: 23455 AN XY: 74230

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.347

Alfa AF: 0.332 Hom.: 5695

Bravo AF: 0.321

Asia WGS AF: 0.334 AC: 1158 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs1316607; hg19: chr12-51042890;