9-124787209-C-T

Position:

• chr9-124787209-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182487.4(OLFML2A):​c.325C>T​(p.Leu109Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLFML2A NM_182487.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2A	NM_182487.4	c.325C>T	p.Leu109Phe	missense_variant	2/8	ENST00000373580.8	NP_872293.2
OLFML2A	XM_006716989.3	c.325C>T	p.Leu109Phe	missense_variant	2/7		XP_006717052.1
OLFML2A	XM_005251760.6	c.325C>T	p.Leu109Phe	missense_variant	2/7		XP_005251817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML2A	ENST00000373580.8	c.325C>T	p.Leu109Phe	missense_variant	2/8	1	NM_182487.4	ENSP00000362682.3
OLFML2A	ENST00000331715.13	c.325C>T	p.Leu109Phe	missense_variant	2/5	2		ENSP00000336425.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461816 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 06, 2024

The c.325C>T (p.L109F) alteration is located in exon 2 (coding exon 2) of the OLFML2A gene. This alteration results from a C to T substitution at nucleotide position 325, causing the leucine (L) at amino acid position 109 to be replaced by a phenylalanine (F). 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	0.44
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.1	.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;D
Vest4		0.62
MutPred		0.29		Gain of methylation at K110 (P = 0.0287);Gain of methylation at K110 (P = 0.0287);
MVP		0.63
MPC		0.54
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.58
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs763674122; hg19: chr9-127549488;