chr1-1338410-T-C

Position:

chr1-1338410-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001330311.2(DVL1):c.1366A>G(p.Thr456Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,612,314 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 12 hom. )

Consequence

DVL1
NM_001330311.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

DVL1 (HGNC:3084): (dishevelled segment polarity protein 1) DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. DVL1 is a candidate gene for neuroblastomatous transformation. The Schwartz-Jampel syndrome and Charcot-Marie-Tooth disease type 2A have been mapped to the same region as DVL1. The phenotypes of these diseases may be consistent with defects which might be expected from aberrant expression of a DVL gene during development. [provided by RefSeq, Jul 2008]

DVL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009426951).

BP6

Variant 1-1338410-T-C is Benign according to our data. Variant chr1-1338410-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DVL1	NM_001330311.2 linkuse as main transcript	c.1366A>G	p.Thr456Ala	missense_variant	13/15	ENST00000378888.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DVL1	ENST00000378888.10 linkuse as main transcript	c.1366A>G	p.Thr456Ala	missense_variant	13/15	5	NM_001330311.2	P3	O14640-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

311

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00210

AC:

522

AN:

248966

Hom.:

AF XY:

0.00205

AC XY:

277

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.000561

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00387

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.00333

AC:

4860

AN:

1460020

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2372

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.00190

Gnomad4 NFE exome

AF:

0.00403

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152294

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00382

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.00202

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00338

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4Other:1

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 20, 2017	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpretted as Likely benign and reported on 01-23-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	DVL1: BP4, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2020	- -

DVL1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 04, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autosomal dominant Robinow syndrome 2;C4551475:Autosomal dominant Robinow syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.29

DANN

Benign

0.73

DEOGEN2

Benign

0.37

.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.46

T;T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.0094

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

.;N;.;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.3

N;N;.;.

REVEL

Benign

0.029

Sift

Benign

0.47

T;T;.;.

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.057

B;B;.;.

Vest4

0.24

MVP

0.49

MPC

0.081

ClinPred

0.0051

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.43

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