rs2839327

Variant names:

• chr21-46562739-G-A
• rs2839327
• NM_015151.4:c.4089+934G>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.4089+934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,098 control chromosomes in the GnomAD database, including 45,849 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 0.77 (45849 hom., cov: 32)
• Consequence: DIP2A NM_015151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 12 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 (AMR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.4089+934G>A		intron_variant	Intron 34 of 37	ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.4089+934G>A		intron_variant	Intron 34 of 37	1	NM_015151.4	ENSP00000392066.2

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117670 AN: 151980 Hom.: 45803 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.774 AC: 117773 AN: 152098 Hom.: 45849 Cov.: 32 AF XY: 0.777 AC XY: 57762 AN XY: 74360

African (AFR) AF: 0.722 AC: 29969 AN: 41488

American (AMR) AF: 0.804 AC: 12306 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2694 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3002 AN: 5140

South Asian (SAS) AF: 0.801 AC: 3848 AN: 4806

European-Finnish (FIN) AF: 0.834 AC: 8834 AN: 10596

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54615 AN: 67976

Other (OTH) AF: 0.764 AC: 1615 AN: 2114

Alfa AF: 0.795 Hom.: 80704

Bravo AF: 0.767

Asia WGS AF: 0.699 AC: 2434 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	0.0060
DANN	Benign	0.45
PhyloP100		-2.7
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: rs2839327; hg19: chr21-47982652;