19-54503727-C-T

Position:

chr19-54503727-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002288.6(LAIR2):c.62C>T(p.Thr21Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

LAIR2
NM_002288.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.447

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03853482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAIR2	NM_002288.6 linkuse as main transcript	c.62C>T	p.Thr21Met	missense_variant	2/5	ENST00000301202.7	NP_002279.2	Q6ISS4-1
LAIR2	NM_021270.5 linkuse as main transcript	c.62C>T	p.Thr21Met	missense_variant	2/4		NP_067154.1	Q6ISS4-2
LAIR2	XM_011526961.3 linkuse as main transcript	c.34+775C>T		intron_variant			XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAIR2	ENST00000301202.7 linkuse as main transcript	c.62C>T	p.Thr21Met	missense_variant	2/5	1	NM_002288.6	ENSP00000301202.2	Q6ISS4-1
LAIR2	ENST00000351841.2 linkuse as main transcript	c.62C>T	p.Thr21Met	missense_variant	2/4	1		ENSP00000301203.2	Q6ISS4-2
LAIR2	ENST00000412608.5 linkuse as main transcript	c.44C>T	p.Thr15Met	missense_variant	2/3	1		ENSP00000390729.1	C9JFQ0
LAIR2	ENST00000610651.1 linkuse as main transcript	c.17-4164C>T		intron_variant		5		ENSP00000484484.1	A0A087X1V4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

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:

0.0000795

AC:

AN:

251444

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Dec 09, 2023

The c.62C>T (p.T21M) alteration is located in exon 2 (coding exon 2) of the LAIR2 gene. This alteration results from a C to T substitution at nucleotide position 62, causing the threonine (T) at amino acid position 21 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

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0033

.;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.00090

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

.;L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.077

Sift

Benign

0.14

T;T;T

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.32

B;B;D

Vest4

0.34, 0.37

MVP

0.38

MPC

0.25

ClinPred

0.011

GERP RS

-0.035

Varity_R

0.018

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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