21-46547064-C-T

Position:

• chr21-46547064-C-T

Variant summary

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

The ENST00000466639.5(DIP2A):​c.*18C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,607,588 control chromosomes in the GnomAD database, including 16,736 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 0.11 (1149 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15587 hom.)
• Consequence: DIP2A ENST00000466639.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

DIP2A (HGNC:17217): (disco interacting protein 2 homolog A) The protein encoded by this gene may be involved in axon patterning in the central nervous system. This gene is not highly expressed. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.2522+22C>T		intron_variant		ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.2522+22C>T		intron_variant		1	NM_015151.4	ENSP00000392066	P4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17080 AN: 152102 Hom.: 1148 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.131 AC: 32280 AN: 246884 Hom.: 2438 AF XY: 0.140 AC XY: 18708 AN XY: 133960

Gnomad AFR exome AF: 0.0396

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.0965

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.141 AC: 204818 AN: 1455368 Hom.: 15587 Cov.: 32 AF XY: 0.144 AC XY: 104125 AN XY: 722692

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.0987

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.112 AC: 17092 AN: 152220 Hom.: 1149 Cov.: 32 AF XY: 0.114 AC XY: 8511 AN XY: 74424

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.115

Alfa AF: 0.125 Hom.: 1333

Bravo AF: 0.103

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs16979358; hg19: chr21-47966977; COSMIC: COSV59475986; COSMIC: COSV59475986;