Variant chr2-174223105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013341.5(OLA1):c.301C>T(p.His101Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OLA1
NM_013341.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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]

OLA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OLA1	NM_013341.5 linkuse as main transcript	c.301C>T	p.His101Tyr	missense_variant	4/11	ENST00000284719.8
OLA1	NM_001328688.2 linkuse as main transcript	c.301C>T	p.His101Tyr	missense_variant	4/11
OLA1	NM_001011708.3 linkuse as main transcript	c.-174C>T		5_prime_UTR_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLA1	ENST00000284719.8 linkuse as main transcript	c.301C>T	p.His101Tyr	missense_variant	4/11	1	NM_013341.5	P1	Q9NTK5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 02, 2022

The c.301C>T (p.H101Y) alteration is located in exon 4 (coding exon 3) of the OLA1 gene. This alteration results from a C to T substitution at nucleotide position 301, causing the histidine (H) at amino acid position 101 to be replaced by a tyrosine (Y). 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

Uncertain

0.53

BayesDel_addAF

Benign

0.00052

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;T;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;.

Polyphen

0.94

P;D;.;.

Vest4

0.60

MutPred

0.78

Loss of disorder (P = 0.0425);Loss of disorder (P = 0.0425);.;Loss of disorder (P = 0.0425);

MVP

0.75

MPC

1.1

ClinPred

0.97

GERP RS

6.2

Varity_R

0.37

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over