rs2609355

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377229.1(DISP1):c.2835A>G(p.Lys945Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,613,742 control chromosomes in the GnomAD database, including 71,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5581 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65837 hom. )

Consequence

DISP1
NM_001377229.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.589

Publications

18 publications found

Variant links:

Genes affected

DISP1 (HGNC:19711): (dispatched RND transporter family member 1) The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]

DISP1 Gene-Disease associations (from GenCC):

holoprosencephaly
Inheritance: AR, AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Illumina

DISP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-223004232-A-G is Benign according to our data. Variant chr1-223004232-A-G is described in ClinVar as Benign. ClinVar VariationId is 262128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.589 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP1	NM_001377229.1 link	c.2835A>G	p.Lys945Lys	synonymous_variant	Exon 9 of 9	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1 link	c.2835A>G	p.Lys945Lys	synonymous_variant	Exon 9 of 9		NM_001377229.1	ENSP00000502357.1		Q96F81

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40348

AN:

151902

Hom.:

5579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.290

AC:

72642

AN:

250874

AF XY:

0.294

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.298

AC:

435005

AN:

1461722

Hom.:

65837

Cov.:

AF XY:

0.298

AC XY:

216858

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.176

AC:

5898

AN:

33478

American (AMR)

AF:

0.295

AC:

13209

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

8141

AN:

26136

East Asian (EAS)

AF:

0.222

AC:

8811

AN:

39698

South Asian (SAS)

AF:

0.314

AC:

27043

AN:

86252

European-Finnish (FIN)

AF:

0.310

AC:

16562

AN:

53390

Middle Eastern (MID)

AF:

0.275

AC:

1585

AN:

5768

European-Non Finnish (NFE)

AF:

0.302

AC:

336323

AN:

1111912

Other (OTH)

AF:

0.289

AC:

17433

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

20348

40695

61043

81390

101738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11056

22112

33168

44224

55280

<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:

0.266

AC:

40362

AN:

152020

Hom.:

5581

Cov.:

AF XY:

0.267

AC XY:

19804

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.184

AC:

7625

AN:

41478

American (AMR)

AF:

0.282

AC:

4318

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1059

AN:

3472

East Asian (EAS)

AF:

0.223

AC:

1146

AN:

5134

South Asian (SAS)

AF:

0.297

AC:

1429

AN:

4806

European-Finnish (FIN)

AF:

0.328

AC:

3457

AN:

10554

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20248

AN:

67964

Other (OTH)

AF:

0.280

AC:

591

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1488

2976

4465

5953

7441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.283

Hom.:

3468

Bravo

AF:

0.260

Asia WGS

AF:

0.249

AC:

868

AN:

3478

EpiCase

AF:

0.298

EpiControl

AF:

0.305

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.86

CADD

Benign

2.3

(source)

DANN

Benign

0.51

PhyloP100

-0.59

Mutation Taster

=97/3

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