chr5-39377028-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001343.4(DAB2):c.1759A>G(p.Thr587Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,614,028 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.015 ( 54 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 65 hom. )
Consequence
DAB2
NM_001343.4 missense
NM_001343.4 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 0.203
Genes affected
DAB2 (HGNC:2662): (DAB adaptor protein 2) This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0025002956).
BP6
?
Variant 5-39377028-T-C is Benign according to our data. Variant chr5-39377028-T-C is described in ClinVar as [Benign]. Clinvar id is 712448.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAB2 | NM_001343.4 | c.1759A>G | p.Thr587Ala | missense_variant | 12/15 | ENST00000320816.11 | |
DAB2 | NM_001244871.2 | c.1696A>G | p.Thr566Ala | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAB2 | ENST00000320816.11 | c.1759A>G | p.Thr587Ala | missense_variant | 12/15 | 1 | NM_001343.4 | P3 | |
DAB2 | ENST00000509337.5 | c.1696A>G | p.Thr566Ala | missense_variant | 10/13 | 1 | A1 | ||
DAB2 | ENST00000545653.5 | c.1696A>G | p.Thr566Ala | missense_variant | 11/14 | 5 | A1 | ||
DAB2 | ENST00000339788.10 | c.1105A>G | p.Thr369Ala | missense_variant | 11/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0155 AC: 2351AN: 152042Hom.: 55 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00417 AC: 1047AN: 251146Hom.: 29 AF XY: 0.00295 AC XY: 401AN XY: 135720
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GnomAD4 exome AF: 0.00158 AC: 2308AN: 1461868Hom.: 65 Cov.: 34 AF XY: 0.00134 AC XY: 977AN XY: 727242
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GnomAD4 genome ? AF: 0.0155 AC: 2357AN: 152160Hom.: 54 Cov.: 32 AF XY: 0.0152 AC XY: 1129AN XY: 74396
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ESP6500AA
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595
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;.
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;B;B
Vest4
MVP
MPC
0.064
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at