19-54507962-A-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_002288.6(LAIR2):c.142A>G(p.Met48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

LAIR2
NM_002288.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.938

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=0.090515226).

BP6

Variant 19-54507962-A-G is Benign according to our data. Variant chr19-54507962-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3866115.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR2	NM_002288.6 link	c.142A>G	p.Met48Val	missense_variant	Exon 3 of 5	ENST00000301202.7	NP_002279.2	Q6ISS4-1
LAIR2	NM_021270.5 link	c.142A>G	p.Met48Val	missense_variant	Exon 3 of 4		NP_067154.1	Q6ISS4-2
LAIR2	XM_011526961.3 link	c.106A>G	p.Met36Val	missense_variant	Exon 2 of 4		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAIR2	ENST00000301202.7 link	c.142A>G	p.Met48Val	missense_variant	Exon 3 of 5	1	NM_002288.6	ENSP00000301202.2	Q6ISS4-1
LAIR2	ENST00000351841.2 link	c.142A>G	p.Met48Val	missense_variant	Exon 3 of 4	1		ENSP00000301203.2	Q6ISS4-2
LAIR2	ENST00000412608.5 link	c.124A>G	p.Met42Val	missense_variant	Exon 3 of 3	1		ENSP00000390729.1	C9JFQ0
LAIR2	ENST00000610651.1 link	c.88A>G	p.Met30Val	missense_variant	Exon 2 of 2	5		ENSP00000484484.1	A0A087X1V4

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251398

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000231

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:

0.0000528

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000718

AC:

105

AN:

1461810

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000145

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000710

Hom.:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.023

DANN

Benign

0.26

DEOGEN2

Benign

0.0036

.;.;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0044

M_CAP

Benign

0.00089

MetaRNN

Benign

0.091

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.9

.;.;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.12

N;.;N;N

REVEL

Benign

0.041

Sift

Benign

0.33

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.067, 0.062

MVP

0.048

MPC

0.22

ClinPred

0.052

GERP RS

-3.6

Varity_R

0.055

gMVP

0.15

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