rs2839290

Positions:

• chr21-46490263-G-A
• chr21-46490263-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.164-337G>A		intron_variant		ENST00000417564.3	NP_055966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3	c.164-337G>A		intron_variant		1	NM_015151.4	ENSP00000392066	P4

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

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.380

Alfa AF: 0.241 Hom.: 563

Bravo AF: 0.346

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2839290; hg19: chr21-47910176;