NM_182487.4:c.20C>G

Variant names:

• chr9-124777290-C-G
• rs980296301
• NM_182487.4:c.20C>G

Variant summary

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

The NM_182487.4(OLFML2A):​c.20C>G​(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000904 in 1,106,490 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. 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. P7A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: OLFML2A NM_182487.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 0 publications found

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

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=0.12721732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182487.4. 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
	OLFML2A	NM_182487.4	MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 8	NP_872293.2	Q68BL7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML2A	ENST00000373580.8	TSL:1 MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 8	ENSP00000362682.3	Q68BL7-1
	OLFML2A	ENST00000928170.1		c.20C>G	p.Pro7Arg	missense	Exon 1 of 7	ENSP00000598229.1
	OLFML2A	ENST00000863982.1		c.20C>G	p.Pro7Arg	missense	Exon 1 of 7	ENSP00000534041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.04e-7 AC: 1 AN: 1106490 Hom.: 0 Cov.: 23 AF XY: 0.00000188 AC XY: 1 AN XY: 531456

African (AFR) AF: 0.00 AC: 0 AN: 23022

American (AMR) AF: 0.00 AC: 0 AN: 13276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16140

East Asian (EAS) AF: 0.00 AC: 0 AN: 25732

South Asian (SAS) AF: 0.00 AC: 0 AN: 31440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3024

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 926466

Other (OTH) AF: 0.00 AC: 0 AN: 44154

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.6
DANN	Benign	0.91
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.91
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.072
Sift	Benign	0.030	D
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.069
MutPred		0.24		Gain of methylation at P7 (P = 0.0078)
MVP		0.11
MPC		0.13
ClinPred		0.16	T
GERP RS		-3.2
PromoterAI		0.087	Neutral
Varity_R		0.048
gMVP		0.39
Mutation Taster		=97/3	polymorphism

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: rs980296301; hg19: chr9-127539569;