21-46547064-C-T

Variant names:

• chr21-46547064-C-T
• rs16979358
• ENST00000466639.5:c.*18C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

DIP2A Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466639.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2A	NM_015151.4	MANE Select	c.2522+22C>T		intron	N/A	NP_055966.2
	DIP2A	NM_206890.3		c.*18C>T		3_prime_UTR	Exon 21 of 21	NP_996773.1
	DIP2A	NM_001146115.2		c.*18C>T		3_prime_UTR	Exon 20 of 20	NP_001139587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2A	ENST00000466639.5	TSL:1	c.*18C>T		3_prime_UTR	Exon 20 of 20	ENSP00000430249.1
	DIP2A	ENST00000417564.3	TSL:1 MANE Select	c.2522+22C>T		intron	N/A	ENSP00000392066.2
	DIP2A	ENST00000457905.7	TSL:1	c.2522+22C>T		intron	N/A	ENSP00000393434.3

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

GnomAD2 exomes AF: 0.131 AC: 32280 AN: 246884 AF XY: 0.140

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 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

African (AFR) AF: 0.0388 AC: 1294 AN: 33386

American (AMR) AF: 0.0641 AC: 2857 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 2573 AN: 26076

East Asian (EAS) AF: 0.109 AC: 4314 AN: 39512

South Asian (SAS) AF: 0.225 AC: 19320 AN: 85920

European-Finnish (FIN) AF: 0.142 AC: 7567 AN: 53216

Middle Eastern (MID) AF: 0.161 AC: 924 AN: 5748

European-Non Finnish (NFE) AF: 0.142 AC: 157712 AN: 1106842

Other (OTH) AF: 0.137 AC: 8257 AN: 60108

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

African (AFR) AF: 0.0409 AC: 1697 AN: 41532

American (AMR) AF: 0.104 AC: 1592 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.117 AC: 608 AN: 5192

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4824

European-Finnish (FIN) AF: 0.138 AC: 1460 AN: 10594

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9954 AN: 68002

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.124 Hom.: 1818

Bravo AF: 0.103

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.59
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16979358; hg19: chr21-47966977; COSMIC: COSV59475986; COSMIC: COSV59475986;