chr21-46490263-G-A

Variant names:

• chr21-46490263-G-A
• rs2839290
• NM_015151.4:c.164-337G>A

Variant summary

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

The NM_015151.4(DIP2A):​c.164-337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,928 control chromosomes in the GnomAD database, including 9,682 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 (9682 hom., cov: 31)
• Consequence: DIP2A NM_015151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015151.4. 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.164-337G>A		intron	N/A	NP_055966.2
	DIP2A	NM_001410751.1		c.164-337G>A		intron	N/A	NP_001397680.1
	DIP2A	NM_001353942.2		c.164-337G>A		intron	N/A	NP_001340871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2A	ENST00000417564.3	TSL:1 MANE Select	c.164-337G>A		intron	N/A	ENSP00000392066.2
	DIP2A	ENST00000457905.7	TSL:1	c.164-337G>A		intron	N/A	ENSP00000393434.3
	DIP2A	ENST00000466639.5	TSL:1	c.164-337G>A		intron	N/A	ENSP00000430249.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53198 AN: 151810 Hom.: 9671 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.350 AC: 53244 AN: 151928 Hom.: 9682 Cov.: 31 AF XY: 0.345 AC XY: 25608 AN XY: 74228

African (AFR) AF: 0.285 AC: 11799 AN: 41432

American (AMR) AF: 0.302 AC: 4621 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2196 AN: 5130

South Asian (SAS) AF: 0.321 AC: 1548 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3612 AN: 10550

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

European-Non Finnish (NFE) AF: 0.393 AC: 26724 AN: 67942

Other (OTH) AF: 0.380 AC: 798 AN: 2102

Alfa AF: 0.244 Hom.: 595

Bravo AF: 0.346

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2839290; hg19: chr21-47910176;