chr1-161983955-G-A

Position:

• chr1-161983955-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015441.3(OLFML2B):​c.1973C>T​(p.Thr658Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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: 1.80

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17317623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFML2B	NM_015441.3	c.1973C>T	p.Thr658Ile	missense_variant	8/8	ENST00000294794.8
OLFML2B	NM_001347700.2	c.1979C>T	p.Thr660Ile	missense_variant	8/8
OLFML2B	NM_001297713.2	c.1976C>T	p.Thr659Ile	missense_variant	8/8
OLFML2B	XM_011509398.3	c.1253C>T	p.Thr418Ile	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8	c.1973C>T	p.Thr658Ile	missense_variant	8/8	1	NM_015441.3	P3

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.1973C>T (p.T658I) alteration is located in exon 8 (coding exon 8) of the OLFML2B gene. This alteration results from a C to T substitution at nucleotide position 1973, causing the threonine (T) at amino acid position 658 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.13	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.18
MutPred		0.50		.;Loss of disorder (P = 0.0114);.;
MVP		0.78
MPC		0.34
ClinPred		0.27	T
GERP RS		2.3
Varity_R		0.036
gMVP		0.43

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: chr1-161953745;