chr12-50504945-G-T

Variant names:

• chr12-50504945-G-T
• rs61927768
• NM_173602.3:c.-196G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173602.3(DIP2B):​c.-196G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 384,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: DIP2B NM_173602.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 13 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2B	NM_173602.3	c.-196G>T		upstream_gene_variant		ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10	c.-196G>T		upstream_gene_variant		5	NM_173602.3	ENSP00000301180.5
DIP2B	ENST00000549620.5	n.-40G>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000260 AC: 1 AN: 384270 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 208164

African (AFR) AF: 0.00 AC: 0 AN: 8206

American (AMR) AF: 0.00 AC: 0 AN: 14388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10216

East Asian (EAS) AF: 0.00 AC: 0 AN: 26372

South Asian (SAS) AF: 0.00 AC: 0 AN: 43504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1634

European-Non Finnish (NFE) AF: 0.00000431 AC: 1 AN: 231918

Other (OTH) AF: 0.00 AC: 0 AN: 22112

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		1.7
PromoterAI		0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs61927768; hg19: chr12-50898728;