Variant 1-57010703-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365792.1(DAB1):c.1660G>T(p.Gly554Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000798 in 1,571,932 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G554S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0043 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

DAB1
NM_001365792.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.12

Variant links:

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 links:

LOC112267900 (HGNC:):

LOC112267900 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008557349).

BP6

Variant 1-57010703-C-A is Benign according to our data. Variant chr1-57010703-C-A is described in ClinVar as [Benign]. Clinvar id is 786991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 653 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1 linkuse as main transcript	c.1660G>T	p.Gly554Cys	missense_variant	14/15	ENST00000371236.7
LOC112267900	XR_007066117.1 linkuse as main transcript	n.11371C>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7 linkuse as main transcript	c.1660G>T	p.Gly554Cys	missense_variant	14/15	5	NM_001365792.1	P1	O75553-6

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00112

AC:

263

AN:

235822

Hom.:

AF XY:

0.000838

AC XY:

107

AN XY:

127700

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000437

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000924

Gnomad OTH exome

AF:

0.000355

GnomAD4 exome

AF:

0.000423

AC:

600

AN:

1419680

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

271

AN XY:

702820

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.000605

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000373

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000506

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00430

AC:

655

AN:

152252

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000537

Hom.:

Bravo

AF:

0.00471

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00132

AC:

160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.97

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.74

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

N;.;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;.;D;D

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.99

D;D;D;D

Vest4

0.49

MVP

0.64

MPC

1.0

ClinPred

0.045

GERP RS

2.1

Varity_R

0.24

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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