chr1-57010787-C-T

Variant names:

• chr1-57010787-C-T
• NM_001365792.1:c.1576G>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.1576G>A​(p.Asp526Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,404,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DAB1 NM_001365792.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10
• 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=0.16509905).

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.1576G>A	p.Asp526Asn	missense	Exon 14 of 15	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1576G>A	p.Asp526Asn	missense	Exon 14 of 15	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1576G>A	p.Asp526Asn	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.1576G>A	p.Asp526Asn	missense	Exon 14 of 15	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1570G>A	p.Asp524Asn	missense	Exon 13 of 14	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1675G>A	p.Asp559Asn	missense	Exon 15 of 15	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1404160 Hom.: 0 Cov.: 29 AF XY: 0.00000144 AC XY: 1 AN XY: 693110

African (AFR) AF: 0.00 AC: 0 AN: 30866

American (AMR) AF: 0.00 AC: 0 AN: 33866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23654

East Asian (EAS) AF: 0.00 AC: 0 AN: 38710

South Asian (SAS) AF: 0.00 AC: 0 AN: 78150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1083302

Other (OTH) AF: 0.00 AC: 0 AN: 57672

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		6.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.049
Sift	Benign	0.058	T
Sift4G	Benign	0.50	T
Polyphen		0.11	B
Vest4		0.32
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.45
MPC		0.47
ClinPred		0.73	D
GERP RS		5.0
Varity_R		0.15
gMVP		0.26
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

hg19: chr1-57476460;