Variant chr21-46551626-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015151.4(DIP2A):c.2840-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,611,488 control chromosomes in the GnomAD database, including 414,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.75 ( 42857 hom., cov: 33)

Exomes 𝑓: 0.71 ( 371600 hom. )

Consequence

DIP2A
NM_015151.4 splice_region, intron

Scores

Splicing: ADA: 0.00006456

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.478

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-46551626-G-A is Benign according to our data. Variant chr21-46551626-G-A is described in ClinVar as [Benign]. Clinvar id is 3060466.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2A	NM_015151.4 link	c.2840-8G>A		splice_region_variant, intron_variant		ENST00000417564.3	NP_055966.2	Q14689-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DIP2A	ENST00000417564.3 link	c.2840-8G>A	splice_region_variant, intron_variant	1	NM_015151.4	ENSP00000392066.2	Q14689-1
DIP2A	ENST00000651436.1 link	c.2840-8G>A	splice_region_variant, intron_variant			ENSP00000498874.1	A0A494C143
DIP2A	ENST00000400274.5 link	c.2828-8G>A	splice_region_variant, intron_variant	5		ENSP00000383133.1	Q14689-6

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113408

AN:

152028

Hom.:

42811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.731

GnomAD3 exomes

AF:

0.708

AC:

174843

AN:

246932

Hom.:

62158

AF XY:

0.704

AC XY:

94363

AN XY:

134004

show subpopulations

Gnomad AFR exome

AF:

0.876

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.639

Gnomad EAS exome

AF:

0.757

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.700

GnomAD4 exome

AF:

0.713

AC:

1039939

AN:

1459342

Hom.:

371600

Cov.:

AF XY:

0.710

AC XY:

515254

AN XY:

725772

show subpopulations

Gnomad4 AFR exome

AF:

0.876

Gnomad4 AMR exome

AF:

0.657

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.728

Gnomad4 SAS exome

AF:

0.682

Gnomad4 FIN exome

AF:

0.666

Gnomad4 NFE exome

AF:

0.716

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.746

AC:

113510

AN:

152146

Hom.:

42857

Cov.:

AF XY:

0.738

AC XY:

54846

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.870

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.619

Gnomad4 EAS

AF:

0.742

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.717

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.727

Hom.:

24878

Bravo

AF:

0.756

Asia WGS

AF:

0.738

AC:

2569

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIP2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.018

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over