Genetic Variant DIP2A:p.Pro333Pro (chr21-46511511-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015151.4(DIP2A):c.999G>A(p.Pro333Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,612,714 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 7 hom. )

Consequence

DIP2A
NM_015151.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.62

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-46511511-G-A is Benign according to our data. Variant chr21-46511511-G-A is described in ClinVar as Benign. ClinVar VariationId is 781523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.62 with no splicing effect.

BS2

High AC in GnomAd4 at 277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIP2A	NM_015151.4 link	c.999G>A	p.Pro333Pro	synonymous_variant	Exon 8 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.999G>A	p.Pro333Pro	synonymous_variant	Exon 8 of 38	1	NM_015151.4	ENSP00000392066.2		Q14689-1

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

277

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00285

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00192

AC:

475

AN:

247036

AF XY:

0.00201

show subpopulations

Gnomad AFR exome

AF:

0.000458

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.000805

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00298

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00251

AC:

3670

AN:

1460444

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1881

AN XY:

726492

show subpopulations

African (AFR)

AF:

0.000480

AC:

AN:

33358

American (AMR)

AF:

0.00164

AC:

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.000538

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00160

AC:

138

AN:

86038

European-Finnish (FIN)

AF:

0.000600

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00294

AC:

3267

AN:

1111432

Other (OTH)

AF:

0.00216

AC:

130

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

212

423

635

846

1058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.00182

AC:

277

AN:

152270

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000938

AC:

AN:

41564

American (AMR)

AF:

0.00144

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00285

AC:

194

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00207

Hom.:

Bravo

AF:

0.00194

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00410

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.027

(source)

DANN

Benign

0.52

PhyloP100

-6.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism

(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