rs1316607

Variant names:

• chr12-50649107-C-A
• rs1316607
• NM_173602.3:c.301+8255C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.86).
• 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 rank	MANE	Protein	UniProt
DIP2B	NM_173602.3	c.301+8255C>A		intron_variant	Intron 3 of 37	ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10	c.301+8255C>A		intron_variant	Intron 3 of 37	5	NM_173602.3	ENSP00000301180.5
DIP2B	ENST00000546719.1	n.49-5904C>A		intron_variant	Intron 1 of 6	1
DIP2B	ENST00000549620.5	n.457+8255C>A		intron_variant	Intron 3 of 7	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

African (AFR) AF: 0.321 AC: 13318 AN: 41426

American (AMR) AF: 0.266 AC: 4054 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1270 AN: 5164

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2772 AN: 10520

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

European-Non Finnish (NFE) AF: 0.342 AC: 23204 AN: 67930

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.331 Hom.: 9934

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
PhyloP100		0.89
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: rs1316607; hg19: chr12-51042890; COSMIC: COSV107373507;