rs2609355

chr1-223004232-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001377229.1(DISP1):c.2835A>G(p.Lys945=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.589

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]

ACMG classification

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	UniProt
DISP1	NM_001377229.1	c.2835A>G	p.Lys945=	synonymous_variant	9/9	ENST00000675850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP1	ENST00000675850.1	c.2835A>G	p.Lys945=	synonymous_variant	9/9		NM_001377229.1	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40348 AN: 151902 Hom.: 5579 Cov.: 32

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

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.: 68 AF XY: 0.298 AC XY: 216858 AN XY: 727136

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.: 32 AF XY: 0.267 AC XY: 19804 AN XY: 74288

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
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	GeneDx	Jan 19, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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

Other links and lift over

dbSNP: rs2609355; hg19: chr1-223177574; COSMIC: COSV52659190;