dbSNP rs2070435: DIP2A:p.Leu693Leu (chr21-46541798-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015151.4(DIP2A):c.2079G>A(p.Leu693Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,613,500 control chromosomes in the GnomAD database, including 90,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 10961 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80010 hom. )

Consequence

DIP2A
NM_015151.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0400

Publications

41 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DIP2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 21-46541798-G-A is Benign according to our data. Variant chr21-46541798-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060508.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4 link	c.2079G>A	p.Leu693Leu	synonymous_variant	Exon 18 of 38	ENST00000417564.3	NP_055966.2	Q14689-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIP2A	ENST00000417564.3 link	c.2079G>A	p.Leu693Leu	synonymous_variant	Exon 18 of 38	1	NM_015151.4	ENSP00000392066.2		Q14689-1

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56034

AN:

151868

Hom.:

10931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.328

AC:

81753

AN:

249152

AF XY:

0.329

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.328

AC:

478794

AN:

1461514

Hom.:

80010

Cov.:

AF XY:

0.327

AC XY:

238017

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.507

AC:

16956

AN:

33474

American (AMR)

AF:

0.233

AC:

10402

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7707

AN:

26130

East Asian (EAS)

AF:

0.438

AC:

17374

AN:

39696

South Asian (SAS)

AF:

0.320

AC:

27570

AN:

86252

European-Finnish (FIN)

AF:

0.308

AC:

16456

AN:

53388

Middle Eastern (MID)

AF:

0.383

AC:

2208

AN:

5768

European-Non Finnish (NFE)

AF:

0.323

AC:

359550

AN:

1111720

Other (OTH)

AF:

0.341

AC:

20571

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

17865

35730

53595

71460

89325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11798

23596

35394

47192

58990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.369

AC:

56116

AN:

151986

Hom.:

10961

Cov.:

AF XY:

0.364

AC XY:

26997

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.498

AC:

20617

AN:

41432

American (AMR)

AF:

0.273

AC:

4168

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1053

AN:

3470

East Asian (EAS)

AF:

0.425

AC:

2195

AN:

5162

South Asian (SAS)

AF:

0.330

AC:

1587

AN:

4814

European-Finnish (FIN)

AF:

0.300

AC:

3169

AN:

10546

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.324

AC:

22025

AN:

67962

Other (OTH)

AF:

0.379

AC:

800

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1757

3513

5270

7026

8783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.334

Hom.:

8315

Bravo

AF:

0.375

Asia WGS

AF:

0.407

AC:

1417

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIP2A-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.78

CADD

Benign

0.95

(source)

DANN

Benign

0.48

PhyloP100

-0.040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over