chr2-174081974-T-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_013341.5(OLA1):c.819A>T(p.Glu273Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
OLA1
NM_013341.5 missense
NM_013341.5 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 3.66
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06488031).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OLA1 | NM_013341.5 | c.819A>T | p.Glu273Asp | missense_variant | 8/11 | ENST00000284719.8 | NP_037473.3 | |
OLA1 | NM_001328688.2 | c.756A>T | p.Glu252Asp | missense_variant | 8/11 | NP_001315617.1 | ||
OLA1 | NM_001011708.3 | c.345A>T | p.Glu115Asp | missense_variant | 7/10 | NP_001011708.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OLA1 | ENST00000284719.8 | c.819A>T | p.Glu273Asp | missense_variant | 8/11 | 1 | NM_013341.5 | ENSP00000284719 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461032Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726842
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74310
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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 submitter | clinical testing | Ambry Genetics | Mar 30, 2024 | The c.819A>T (p.E273D) alteration is located in exon 8 (coding exon 7) of the OLA1 gene. This alteration results from a A to T substitution at nucleotide position 819, causing the glutamic acid (E) at amino acid position 273 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
Loss of disorder (P = 0.1147);.;.;
MVP
MPC
ClinPred
D
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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