NM_001365792.1:c.1472C>G

Variant names:

• chr1-57011245-G-C
• NM_001365792.1:c.1472C>G

Variant summary

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

The NM_001365792.1(DAB1):​c.1472C>G​(p.Ser491Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DAB1 NM_001365792.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.17
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1472C>G	p.Ser491Cys	missense	Exon 13 of 15	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1472C>G	p.Ser491Cys	missense	Exon 13 of 15	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1472C>G	p.Ser491Cys	missense	Exon 13 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.1472C>G	p.Ser491Cys	missense	Exon 13 of 15	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1466C>G	p.Ser489Cys	missense	Exon 12 of 14	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1571C>G	p.Ser524Cys	missense	Exon 14 of 15	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.90	L
PhyloP100		9.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.24		Loss of phosphorylation at S524 (P = 5e-04)
MVP		0.50
MPC		1.0
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.37
gMVP		0.48
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

hg19: chr1-57476918;