chr1-161984884-T-A

Position:

• chr1-161984884-T-A

Variant summary

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

The NM_015441.3(OLFML2B):​c.1571A>T​(p.Lys524Met) 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 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0700

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/exons	MANE	UniProt
OLFML2B	NM_015441.3	c.1571A>T	p.Lys524Met	missense_variant	7/8	ENST00000294794.8
OLFML2B	NM_001347700.2	c.1577A>T	p.Lys526Met	missense_variant	7/8
OLFML2B	NM_001297713.2	c.1574A>T	p.Lys525Met	missense_variant	7/8
OLFML2B	XM_011509398.3	c.851A>T	p.Lys284Met	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8	c.1571A>T	p.Lys524Met	missense_variant	7/8	1	NM_015441.3	P3
OLFML2B	ENST00000367940.2	c.1574A>T	p.Lys525Met	missense_variant	7/8	2		A2
OLFML2B	ENST00000367938.1	c.20A>T	p.Lys7Met	missense_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 27

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

Apr 17, 2024

The c.1571A>T (p.K524M) alteration is located in exon 7 (coding exon 7) of the OLFML2B gene. This alteration results from a A to T substitution at nucleotide position 1571, causing the lysine (K) at amino acid position 524 to be replaced by a methionine (M). 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	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0060	D;D;T
Sift4G	Uncertain	0.029	D;D;T
Polyphen		0.95	P;P;.
Vest4		0.48
MutPred		0.44		.;Loss of methylation at K525 (P = 0.0016);.;
MVP		0.84
MPC		0.62
ClinPred		0.96	D
GERP RS		3.2
Varity_R		0.28
gMVP		0.62

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: chr1-161954674;