chr2-174082017-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013341.5(OLA1):ā€‹c.776T>Cā€‹(p.Leu259Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,464 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

OLA1
NM_013341.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98
Variant links:
Genes affected
OLA1 (HGNC:28833): (Obg like ATPase 1) This gene encodes a member of the GTPase protein family. The encoded protein interacts with breast cancer-associated gene 1 (BRCA1) and BRCA1-associated RING domain protein (BARD1), and is involved in centrosome regulation. Overexpression of this gene has been observed in multiple types of cancer and may be associated with poor survival. Pseudogenes of this gene have been defined on chromosomes 17 and 22. [provided by RefSeq, Jun 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10278478).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OLA1NM_013341.5 linkuse as main transcriptc.776T>C p.Leu259Ser missense_variant 8/11 ENST00000284719.8 NP_037473.3
OLA1NM_001011708.3 linkuse as main transcriptc.302T>C p.Leu101Ser missense_variant 7/10 NP_001011708.1
OLA1NM_001328688.2 linkuse as main transcriptc.729-16T>C splice_polypyrimidine_tract_variant, intron_variant NP_001315617.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OLA1ENST00000284719.8 linkuse as main transcriptc.776T>C p.Leu259Ser missense_variant 8/111 NM_013341.5 ENSP00000284719 P1Q9NTK5-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251284
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461216
Hom.:
0
Cov.:
30
AF XY:
0.0000303
AC XY:
22
AN XY:
726928
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 06, 2023The c.776T>C (p.L259S) alteration is located in exon 8 (coding exon 7) of the OLA1 gene. This alteration results from a T to C substitution at nucleotide position 776, causing the leucine (L) at amino acid position 259 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T;.;T;T
Eigen
Benign
-0.053
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.53
N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.40
T;T;T;T
Sift4G
Benign
0.74
T;T;T;T
Polyphen
0.0010
B;B;.;.
Vest4
0.64
MutPred
0.37
Gain of phosphorylation at L259 (P = 0.0684);.;.;.;
MVP
0.35
MPC
0.49
ClinPred
0.084
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376243604; hg19: chr2-174946745; API