2-174081927-T-G

Variant names:

• chr2-174081927-T-G
• rs764649077
• NM_013341.5:c.866A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013341.5(OLA1):​c.866A>C​(p.Gln289Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,398 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q289R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OLA1 NM_013341.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLA1	NM_013341.5	MANE Select	c.866A>C	p.Gln289Pro	missense	Exon 8 of 11	NP_037473.3
	OLA1	NM_001328688.2		c.803A>C	p.Gln268Pro	missense	Exon 8 of 11	NP_001315617.1
	OLA1	NM_001011708.3		c.392A>C	p.Gln131Pro	missense	Exon 7 of 10	NP_001011708.1	Q9NTK5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLA1	ENST00000284719.8	TSL:1 MANE Select	c.866A>C	p.Gln289Pro	missense	Exon 8 of 11	ENSP00000284719.3	Q9NTK5-1
	OLA1	ENST00000428402.6	TSL:1	c.729-6400A>C		intron	N/A	ENSP00000410385.2	Q9NTK5-3
	OLA1	ENST00000409546.5	TSL:5	c.926A>C	p.Gln309Pro	missense	Exon 8 of 11	ENSP00000386350.1	J3KQ32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459398 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726048

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111258

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Benign	0.17	T
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.67
MutPred		0.58		Gain of loop (P = 0.069)
MVP		0.49
MPC		0.44
ClinPred		0.40	T
GERP RS		5.9
Varity_R		0.54
gMVP		0.97
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs764649077; hg19: chr2-174946655;