GeneBe

rs758259305

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006403.4(NEDD9):​c.2038G>T​(p.Val680Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,888 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.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NEDD9
NM_006403.4 missense

Scores

3
6
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.75
Variant links:
Genes affected
NEDD9 (HGNC:7733): (neural precursor cell expressed, developmentally down-regulated 9) The protein encoded by this gene is a member of the CRK-associated substrates family. Members of this family are adhesion docking molecules that mediate protein-protein interactions for signal transduction pathways. This protein is a focal adhesion protein that acts as a scaffold to regulate signaling complexes important in cell attachment, migration and invasion as well as apoptosis and the cell cycle. This protein has also been reported to have a role in cancer metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3609538).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEDD9NM_006403.4 linkc.2038G>T p.Val680Leu missense_variant Exon 7 of 7 ENST00000379446.10 NP_006394.1 Q14511-1
NEDD9NM_001142393.2 linkc.2038G>T p.Val680Leu missense_variant Exon 8 of 8 NP_001135865.1 Q14511-3A0A024QZV9
NEDD9NM_001271033.2 linkc.1591G>T p.Val531Leu missense_variant Exon 6 of 6 NP_001257962.1 Q14511A0A087WUD2
NEDD9NR_073131.1 linkn.2645G>T non_coding_transcript_exon_variant Exon 10 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEDD9ENST00000379446.10 linkc.2038G>T p.Val680Leu missense_variant Exon 7 of 7 1 NM_006403.4 ENSP00000368759.5 Q14511-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461888
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.36
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.;L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.3
N;.;N
REVEL
Benign
0.23
Sift
Uncertain
0.0080
D;.;D
Sift4G
Uncertain
0.050
T;D;T
Polyphen
1.0
D;.;.
Vest4
0.48
MutPred
0.091
Gain of catalytic residue at V680 (P = 0.2104);.;Gain of catalytic residue at V680 (P = 0.2104);
MVP
0.47
MPC
0.62
ClinPred
0.90
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.13
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-11185862; API