2-174123669-T-G

Variant names:

• chr2-174123669-T-G
• NM_013341.5:c.556A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013341.5(OLA1):​c.556A>C​(p.Met186Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,414,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: OLA1 NM_013341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17149225).

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.556A>C	p.Met186Leu	missense	Exon 6 of 11	NP_037473.3
	OLA1	NM_001328688.2		c.556A>C	p.Met186Leu	missense	Exon 6 of 11	NP_001315617.1
	OLA1	NM_001011708.3		c.82A>C	p.Met28Leu	missense	Exon 5 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.556A>C	p.Met186Leu	missense	Exon 6 of 11	ENSP00000284719.3	Q9NTK5-1
	OLA1	ENST00000428402.6	TSL:1	c.556A>C	p.Met186Leu	missense	Exon 6 of 8	ENSP00000410385.2	Q9NTK5-3
	OLA1	ENST00000409546.5	TSL:5	c.616A>C	p.Met206Leu	missense	Exon 6 of 11	ENSP00000386350.1	J3KQ32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1414758 Hom.: 0 Cov.: 24 AF XY: 0.00000283 AC XY: 2 AN XY: 705490

African (AFR) AF: 0.00 AC: 0 AN: 32022

American (AMR) AF: 0.00 AC: 0 AN: 39668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25390

East Asian (EAS) AF: 0.00 AC: 0 AN: 38612

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081536

Other (OTH) AF: 0.0000171 AC: 1 AN: 58526

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3472

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.60
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.060
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		8.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.75	N
REVEL	Benign	0.26
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.68
MutPred		0.53		Gain of helix (P = 0.0078)
MVP		0.35
MPC		0.33
ClinPred		0.37	T
GERP RS		5.4
Varity_R		0.50
gMVP		0.86
Mutation Taster		=19/81	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

hg19: chr2-174988397;