Genetic Variant CD300LB:p.Lys47Arg (chr17-74525978-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_174892.4(CD300LB):c.140A>G(p.Lys47Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD300LB
NM_174892.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

CD300LB (HGNC:30811): (CD300 molecule like family member b) CD300LB is a nonclassical activating receptor of the immunoglobulin (Ig) superfamily expressed on myeloid cells (Martinez-Barriocanal and Sayos, 2006 [PubMed 16920917]).[supplied by OMIM, Mar 2008]

CD300LB links:

LOC107985074 (HGNC:):

LOC107985074 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD300LB	NM_174892.4 link	c.140A>G	p.Lys47Arg	missense_variant	Exon 2 of 4	ENST00000392621.6	NP_777552.3	A8K4G0
CD300LB	XM_005257027.4 link	c.251A>G	p.Lys84Arg	missense_variant	Exon 2 of 4		XP_005257084.1
LOC107985074	XR_007065902.1 link	n.352+4596T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD300LB	ENST00000392621.6 link	c.140A>G	p.Lys47Arg	missense_variant	Exon 2 of 4	1	NM_174892.4	ENSP00000376397.2		A8K4G0
CD300LB	ENST00000314401.3 link	c.140A>G	p.Lys47Arg	missense_variant	Exon 2 of 3	2		ENSP00000317337.4		J9JID3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.251A>G (p.K84R) alteration is located in exon 2 (coding exon 2) of the CD300LB gene. This alteration results from a A to G substitution at nucleotide position 251, causing the lysine (K) at amino acid position 84 to be replaced by an arginine (R). 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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.86

DEOGEN2

Uncertain

0.78

D;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

4.2

H;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

D;.

REVEL

Uncertain

0.44

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;.

Vest4

0.75

MutPred

0.71

Loss of methylation at K47 (P = 0.0106);Loss of methylation at K47 (P = 0.0106);

MVP

0.72

MPC

0.82

ClinPred

0.98

GERP RS

5.0

Varity_R

0.28

gMVP

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over