chr2-174123642-C-T

Variant names:

• chr2-174123642-C-T
• rs1336817737
• NM_013341.5:c.583G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_013341.5(OLA1):​c.583G>A​(p.Asp195Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,445,284 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: OLA1 NM_013341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23188487).

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.583G>A	p.Asp195Asn	missense	Exon 6 of 11	NP_037473.3
	OLA1	NM_001328688.2		c.583G>A	p.Asp195Asn	missense	Exon 6 of 11	NP_001315617.1
	OLA1	NM_001011708.3		c.109G>A	p.Asp37Asn	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.583G>A	p.Asp195Asn	missense	Exon 6 of 11	ENSP00000284719.3	Q9NTK5-1
	OLA1	ENST00000428402.6	TSL:1	c.583G>A	p.Asp195Asn	missense	Exon 6 of 8	ENSP00000410385.2	Q9NTK5-3
	OLA1	ENST00000409546.5	TSL:5	c.643G>A	p.Asp215Asn	missense	Exon 6 of 11	ENSP00000386350.1	J3KQ32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240464 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000692 AC: 10 AN: 1445284 Hom.: 0 Cov.: 28 AF XY: 0.00000695 AC XY: 5 AN XY: 719206

African (AFR) AF: 0.0000305 AC: 1 AN: 32750

American (AMR) AF: 0.00 AC: 0 AN: 41250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 38920

South Asian (SAS) AF: 0.00 AC: 0 AN: 82862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52952

Middle Eastern (MID) AF: 0.000526 AC: 3 AN: 5708

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1105390

Other (OTH) AF: 0.0000335 AC: 2 AN: 59642

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.072
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L
PhyloP100		7.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.061
Sift	Benign	0.068	T
Sift4G	Benign	0.17	T
Polyphen		0.015	B
Vest4		0.71
MutPred		0.44		Gain of sheet (P = 0.0011)
MVP		0.49
MPC		0.42
ClinPred		0.38	T
GERP RS		5.4
Varity_R		0.34
gMVP		0.77
Mutation Taster		=48/52	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: rs1336817737; hg19: chr2-174988370;