rs375940905

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365792.1(DAB1):​c.1276G>T​(p.Val426Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V426M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DAB1
NM_001365792.1 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19433928).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DAB1NM_001365792.1 linkc.1276G>T p.Val426Leu missense_variant Exon 12 of 15 ENST00000371236.7 NP_001352721.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DAB1ENST00000371236.7 linkc.1276G>T p.Val426Leu missense_variant Exon 12 of 15 5 NM_001365792.1 ENSP00000360280.1 O75553-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461836
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
.;.;.;T
Eigen
Benign
0.11
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.86
.;D;D;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.1
.;.;.;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.5
N;.;N;N
REVEL
Benign
0.081
Sift
Benign
0.13
T;.;T;T
Sift4G
Uncertain
0.049
D;D;T;D
Polyphen
0.15
B;B;P;P
Vest4
0.47
MutPred
0.18
.;.;.;Gain of glycosylation at P456 (P = 0.1094);
MVP
0.51
MPC
0.33
ClinPred
0.84
D
GERP RS
4.6
Varity_R
0.26
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-57480724; API