12-50505023-GGTGCTGGTGGTGCTCGGCGGCCGGAGCCGGATCCTGTAGCCGGGTGTGGGCCCGTGTCTGTCCGTCCCTCCTTCGGCCCCCTCTCTTGTCTTCCGGAGTGTGGCTGGCGGAGCTGGGATGGCGGAACGAGGCCTGGAGCCGTCGCCGGCC-G

Position:

• chr12-50505023-GGTGCTGGTGGTGCTCGGCGGCCGGAGCCGGATCCTGTAGCCGGGTGTGGGCCCGTGTCTGTCCGTCCCTCCTTCGGCCCCCTCTCTTGTCTTCCGGAGTGTGGCTGGCGGAGCTGGGATGGCGGAACGAGGCCTGGAGCCGTCGCCGGCC-G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_173602.3(DIP2B):​c.-116_34del variant causes a start lost, 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: DIP2B NM_173602.3 start_lost, 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIP2B	NM_173602.3	c.-116_34del		start_lost, 5_prime_UTR_variant	1/38	ENST00000301180.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIP2B	ENST00000301180.10	c.-116_34del		start_lost, 5_prime_UTR_variant	1/38	5	NM_173602.3	P1
DIP2B	ENST00000549620.5	n.41_190del		non_coding_transcript_exon_variant	1/8	1

Frequencies

GnomAD3 genomes Cov.: 27

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

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

DIP2B: PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50898806;