rs61927768

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-50504945-G-A
• chr12-50504945-G-C
• chr12-50504945-G-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.-196G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 533,844 control chromosomes in the GnomAD database, including 31,510 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 0.20 (3824 hom., cov: 32)
  • Exomes 𝑓: 0.30 (27686 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173602.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2B	NM_173602.3	MANE Select	c.-196G>A		upstream_gene	N/A	NP_775873.2	Q9P265

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2B	ENST00000301180.10	TSL:5 MANE Select	c.-196G>A		upstream_gene	N/A	ENSP00000301180.5	Q9P265
	DIP2B	ENST00000549620.5	TSL:1	n.-40G>A		upstream_gene	N/A
	DIP2B	ENST00000869771.1		c.-196G>A		upstream_gene	N/A	ENSP00000539830.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 29843 AN: 149824 Hom.: 3824 Cov.: 32

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.301 AC: 115416 AN: 383896 Hom.: 27686 Cov.: 4 AF XY: 0.300 AC XY: 62368 AN XY: 207948

African (AFR) AF: 0.0608 AC: 499 AN: 8202

American (AMR) AF: 0.174 AC: 2508 AN: 14378

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 2406 AN: 10210

East Asian (EAS) AF: 0.0692 AC: 1824 AN: 26352

South Asian (SAS) AF: 0.279 AC: 12144 AN: 43490

European-Finnish (FIN) AF: 0.295 AC: 7640 AN: 25894

Middle Eastern (MID) AF: 0.294 AC: 479 AN: 1632

European-Non Finnish (NFE) AF: 0.352 AC: 81467 AN: 231652

Other (OTH) AF: 0.292 AC: 6449 AN: 22086

GnomAD4 genome AF: 0.199 AC: 29837 AN: 149948 Hom.: 3824 Cov.: 32 AF XY: 0.195 AC XY: 14292 AN XY: 73224

African (AFR) AF: 0.0560 AC: 2307 AN: 41200

American (AMR) AF: 0.166 AC: 2499 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 591 AN: 3380

East Asian (EAS) AF: 0.0610 AC: 315 AN: 5164

South Asian (SAS) AF: 0.242 AC: 1152 AN: 4758

European-Finnish (FIN) AF: 0.240 AC: 2474 AN: 10292

Middle Eastern (MID) AF: 0.221 AC: 61 AN: 276

European-Non Finnish (NFE) AF: 0.296 AC: 19811 AN: 66902

Other (OTH) AF: 0.224 AC: 465 AN: 2078

Alfa AF: 0.127 Hom.: 247

Bravo AF: 0.184

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		1.7
PromoterAI		0.023	Neutral
Mutation Taster		=99/1	polymorphism

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; COSMIC: COSV56594422;