9-124787038-A-C

Position:

• chr9-124787038-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182487.4(OLFML2A):​c.154A>C​(p.Ile52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: OLFML2A NM_182487.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

Genes affected

OLFML2A (HGNC:27270): (olfactomedin like 2A) Predicted to enable extracellular matrix binding activity and identical protein binding activity. Predicted to act upstream of or within extracellular matrix organization. Predicted to be located in extracellular matrix and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34988552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2A	NM_182487.4	c.154A>C	p.Ile52Leu	missense_variant	2/8	ENST00000373580.8	NP_872293.2
OLFML2A	XM_006716989.3	c.154A>C	p.Ile52Leu	missense_variant	2/7		XP_006717052.1
OLFML2A	XM_005251760.6	c.154A>C	p.Ile52Leu	missense_variant	2/7		XP_005251817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML2A	ENST00000373580.8	c.154A>C	p.Ile52Leu	missense_variant	2/8	1	NM_182487.4	ENSP00000362682	P2
OLFML2A	ENST00000331715.13	c.154A>C	p.Ile52Leu	missense_variant	2/5	2		ENSP00000336425

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.154A>C (p.I52L) alteration is located in exon 2 (coding exon 2) of the OLFML2A gene. This alteration results from a A to C substitution at nucleotide position 154, causing the isoleucine (I) at amino acid position 52 to be replaced by a leucine (L). 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	Benign	0.15
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	.;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.13
Sift	Benign	0.083	T;T
Sift4G	Uncertain	0.014	D;T
Polyphen		0.99	D;D
Vest4		0.31
MutPred		0.30		Gain of catalytic residue at I52 (P = 0.0138);Gain of catalytic residue at I52 (P = 0.0138);
MVP		0.30
MPC		0.26
ClinPred		0.79	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.40

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.

Other links and lift over

hg19: chr9-127549317;