1-57010757-G-T

Variant names:

• chr1-57010757-G-T
• rs779432585
• NM_001365792.1:c.1606C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365792.1(DAB1):​c.1606C>A​(p.Pro536Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P536A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DAB1 NM_001365792.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 37

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

LOC112267900 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2165373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001365792.1	MANE Select	c.1606C>A	p.Pro536Thr	missense	Exon 14 of 15	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1606C>A	p.Pro536Thr	missense	Exon 14 of 15	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1606C>A	p.Pro536Thr	missense	Exon 14 of 15	NP_001340914.1	O75553-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.1606C>A	p.Pro536Thr	missense	Exon 14 of 15	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1600C>A	p.Pro534Thr	missense	Exon 13 of 14	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1705C>A	p.Pro569Thr	missense	Exon 15 of 15	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444534 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716314

African (AFR) AF: 0.00 AC: 0 AN: 32864

American (AMR) AF: 0.00 AC: 0 AN: 43234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25698

East Asian (EAS) AF: 0.00 AC: 0 AN: 39230

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101030

Other (OTH) AF: 0.00 AC: 0 AN: 59510

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.035	D
Polyphen		0.95	P
Vest4		0.55
MutPred		0.26		Gain of phosphorylation at P569 (P = 0.0062)
MVP		0.71
MPC		0.48
ClinPred		0.69	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.54
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs779432585; hg19: chr1-57476430;