19-9857758-C-A

Variant names:

• chr19-9857758-C-A
• rs2303100
• NM_058164.4:c.317G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058164.4(OLFM2):​c.317G>T​(p.Arg106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R106Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2944405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058164.4. 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
	OLFM2	NM_058164.4	MANE Select	c.317G>T	p.Arg106Leu	missense	Exon 3 of 6	NP_477512.1	O95897
	OLFM2	NM_001304347.2		c.389G>T	p.Arg130Leu	missense	Exon 3 of 6	NP_001291276.1	K7EKW2
	OLFM2	NM_001304348.2		c.83G>T	p.Arg28Leu	missense	Exon 2 of 5	NP_001291277.1	K7EIS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM2	ENST00000264833.9	TSL:1 MANE Select	c.317G>T	p.Arg106Leu	missense	Exon 3 of 6	ENSP00000264833.3	O95897
	OLFM2	ENST00000593091.2	TSL:5	c.389G>T	p.Arg130Leu	missense	Exon 3 of 6	ENSP00000465809.2	K7EKW2
	OLFM2	ENST00000971550.1		c.311G>T	p.Arg104Leu	missense	Exon 3 of 6	ENSP00000641609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.0046
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.63
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.010	D
Polyphen		0.75	P
Vest4		0.39
MutPred		0.38		Loss of methylation at R106 (P = 0.0365)
MVP		0.068
MPC		1.0
ClinPred		0.81	D
GERP RS		3.9
PromoterAI		0.036	Neutral
Varity_R		0.20
Mutation Taster		=89/11	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: rs2303100; hg19: chr19-9968434;