1-57015223-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001365792.1(DAB1):c.1104C>T(p.Pro368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,614,042 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (10 hom.)
• Consequence: DAB1 NM_001365792.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.882

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-57015223-G-A is Benign according to our data. Variant chr1-57015223-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57015223-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.882 with no splicing effect.
• BS2: High AC in GnomAd at 336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.1104C>T	p.Pro368=	synonymous_variant	12/15	ENST00000371236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.1104C>T	p.Pro368=	synonymous_variant	12/15	5	NM_001365792.1	P1

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 152154 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00839

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00240 AC: 602 AN: 251208 Hom.: 1 AF XY: 0.00219 AC XY: 297 AN XY: 135754

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0133

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00198 AC: 2899 AN: 1461770 Hom.: 10 Cov.: 32 AF XY: 0.00198 AC XY: 1439 AN XY: 727174

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00221 AC: 336 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74464

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00839

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00264 Hom.: 0

Bravo AF: 0.00148

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00154

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	DAB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	12
Dann	Benign	0.83

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: rs148158311; hg19: chr1-57480896;