rs201760376

Variant names:

• chr9-124787179-C-T
• rs201760376
• NM_182487.4:c.295C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_182487.4(OLFML2A):​c.295C>T​(p.Pro99Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: OLFML2A NM_182487.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 4 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 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

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.295C>T	p.Pro99Ser	missense	Exon 2 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.295C>T	p.Pro99Ser	missense	Exon 2 of 8	ENSP00000362682.3	Q68BL7-1
	OLFML2A	ENST00000928170.1		c.295C>T	p.Pro99Ser	missense	Exon 2 of 7	ENSP00000598229.1
	OLFML2A	ENST00000863982.1		c.295C>T	p.Pro99Ser	missense	Exon 2 of 7	ENSP00000534041.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000164 AC: 41 AN: 249352 AF XY: 0.000155

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000319 AC: 467 AN: 1461778 Hom.: 0 Cov.: 32 AF XY: 0.000316 AC XY: 230 AN XY: 727194

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000388 AC: 431 AN: 1111912

Other (OTH) AF: 0.000364 AC: 22 AN: 60392

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74366

African (AFR) AF: 0.0000724 AC: 3 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000238 Hom.: 0

Bravo AF: 0.000170

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000238 AC: 1

ESP6500EA AF: 0.000355 AC: 3

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MVP		0.61
MPC		0.57
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.82
gMVP		0.60
Mutation Taster		=32/68	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: rs201760376; hg19: chr9-127549458;