Variant rs2609355 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
DISP1	NM_001377229.1 linkuse as main transcript	c.2835A>G	p.Lys945Lys	synonymous_variant	9/9	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1 linkuse as main transcript	c.2835A>G	p.Lys945Lys	synonymous_variant	9/9		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

GnomAD3 exomes

AF:

0.290

AC:

72642

AN:

250874

Hom.:

10687

AF XY:

0.294

AC XY:

39911

AN XY:

135572

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 SAS exome

AF:

0.312

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

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.266

AC:

40362

AN:

152020

Hom.:

5581

Cov.:

AF XY:

0.267

AC XY:

19804

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.280

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

DANN

Benign

0.51

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

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