Variant 19-54508128-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002288.6(LAIR2):c.308A>G(p.Tyr103Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

LAIR2
NM_002288.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

LAIR2 (HGNC:6478): (leukocyte associated immunoglobulin like receptor 2) The protein encoded by this gene is a member of the immunoglobulin superfamily. It was identified by its similarity to leukocyte-associated immunoglobulin-like receptor 1, a membrane-bound receptor that modulates innate immune response. The protein encoded by this locus is a soluble receptor that may play roles in both inhibition of collagen-induced platelet aggregation and vessel formation during placental implantation. This gene maps to a region of 19q13.4, termed the leukocyte receptor cluster, which contains 29 genes in the immunoglobulin superfamily. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2013]

LAIR2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
LAIR2	NM_002288.6 linkuse as main transcript	c.308A>G	p.Tyr103Cys	missense_variant	3/5	ENST00000301202.7	NP_002279.2	Q6ISS4-1
LAIR2	NM_021270.5 linkuse as main transcript	c.308A>G	p.Tyr103Cys	missense_variant	3/4		NP_067154.1	Q6ISS4-2
LAIR2	XM_011526961.3 linkuse as main transcript	c.272A>G	p.Tyr91Cys	missense_variant	2/4		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAIR2	ENST00000301202.7 linkuse as main transcript	c.308A>G	p.Tyr103Cys	missense_variant	3/5	1	NM_002288.6	ENSP00000301202.2	Q6ISS4-1
LAIR2	ENST00000351841.2 linkuse as main transcript	c.308A>G	p.Tyr103Cys	missense_variant	3/4	1		ENSP00000301203.2	Q6ISS4-2
LAIR2	ENST00000412608.5 linkuse as main transcript	c.*22A>G		downstream_gene_variant		1		ENSP00000390729.1	C9JFQ0
LAIR2	ENST00000610651.1 linkuse as main transcript	c.*22A>G		downstream_gene_variant		5		ENSP00000484484.1	A0A087X1V4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250994

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000687

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.308A>G (p.Y103C) alteration is located in exon 3 (coding exon 3) of the LAIR2 gene. This alteration results from a A to G substitution at nucleotide position 308, causing the tyrosine (Y) at amino acid position 103 to be replaced by a cysteine (C). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.23

M_CAP

Benign

0.0042

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-8.1

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.84

P;D

Vest4

0.49

MVP

0.27

MPC

0.88

ClinPred

0.96

GERP RS

-2.3

Varity_R

0.46

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over