chr21-46478054-C-T

Variant names:

• chr21-46478054-C-T
• rs2839281
• NM_015151.4:c.92-6703C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015151.4(DIP2A):​c.92-6703C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,982 control chromosomes in the GnomAD database, including 9,709 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 0.35 (9709 hom., cov: 31)
• Consequence: DIP2A NM_015151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.92-6703C>T		intron_variant	Intron 1 of 37	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.92-6703C>T		intron_variant	Intron 1 of 37	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53287 AN: 151864 Hom.: 9698 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.351 AC: 53333 AN: 151982 Hom.: 9709 Cov.: 31 AF XY: 0.346 AC XY: 25679 AN XY: 74306

African (AFR) AF: 0.285 AC: 11815 AN: 41440

American (AMR) AF: 0.303 AC: 4626 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3464

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5160

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4826

European-Finnish (FIN) AF: 0.342 AC: 3614 AN: 10552

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26750 AN: 67964

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.362 Hom.: 1320

Bravo AF: 0.347

Asia WGS AF: 0.364 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.29
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2839281; hg19: chr21-47897967;