1-161983694-T-A

Variant names:

• chr1-161983694-T-A
• NM_015441.3:c.2234A>T

Variant summary

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

The NM_015441.3(OLFML2B):​c.2234A>T​(p.His745Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

Genes affected

OLFML2B (HGNC:24558): (olfactomedin like 2B) This gene encodes an olfactomedin domain-containing protein. Most olfactomedin domain-containing proteins are secreted glycoproteins. [provided by RefSeq, Dec 2016]

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 rank	MANE	Protein	UniProt
OLFML2B	NM_015441.3	c.2234A>T	p.His745Leu	missense_variant	Exon 8 of 8	ENST00000294794.8	NP_056256.1
OLFML2B	NM_001347700.2	c.2240A>T	p.His747Leu	missense_variant	Exon 8 of 8		NP_001334629.1
OLFML2B	NM_001297713.2	c.2237A>T	p.His746Leu	missense_variant	Exon 8 of 8		NP_001284642.1
OLFML2B	XM_011509398.3	c.1514A>T	p.His505Leu	missense_variant	Exon 5 of 5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFML2B	ENST00000294794.8	c.2234A>T	p.His745Leu	missense_variant	Exon 8 of 8	1	NM_015441.3	ENSP00000294794.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2234A>T (p.H745L) alteration is located in exon 8 (coding exon 8) of the OLFML2B gene. This alteration results from a A to T substitution at nucleotide position 2234, causing the histidine (H) at amino acid position 745 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	0.25
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	D;D;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Uncertain	0.60
Sift	Benign	0.084	T;T;D
Sift4G	Benign	0.20	T;T;D
Polyphen		0.80	P;P;.
Vest4		0.49
MutPred		0.54		.;Loss of disorder (P = 0.0036);.;
MVP		0.88
MPC		0.52
ClinPred		0.85	D
GERP RS		4.2
Varity_R		0.22
gMVP		0.39

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: chr1-161953484;