rs9979962

Positions:

• chr21-46548394-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015151.4(DIP2A):​c.2522+1352G>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 152,090 control chromosomes in the GnomAD database, including 45,965 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 (45965 hom., cov: 32)
• Consequence: DIP2A NM_015151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2A	NM_015151.4	c.2522+1352G>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.2522+1352G>A		intron_variant		1	NM_015151.4	ENSP00000392066	P4
DIP2A	ENST00000457905.7	c.2522+1352G>A		intron_variant		1		ENSP00000393434
DIP2A	ENST00000400274.5	c.2510+1352G>A		intron_variant		5		ENSP00000383133	A2
DIP2A	ENST00000651436.1	c.2522+1352G>A		intron_variant				ENSP00000498874	A1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117610 AN: 151972 Hom.: 45923 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.774 AC: 117711 AN: 152090 Hom.: 45965 Cov.: 32 AF XY: 0.768 AC XY: 57073 AN XY: 74354

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.760

Alfa AF: 0.746 Hom.: 39379

Bravo AF: 0.778

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9979962; hg19: chr21-47968307; COSMIC: COSV59487879; COSMIC: COSV59487879;