Variant 19-54507974-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002288.6(LAIR2):c.154C>T(p.Pro52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

LAIR2
NM_002288.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.828

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12857029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAIR2	NM_002288.6 linkuse as main transcript	c.154C>T	p.Pro52Ser	missense_variant	3/5	ENST00000301202.7	NP_002279.2	Q6ISS4-1
LAIR2	NM_021270.5 linkuse as main transcript	c.154C>T	p.Pro52Ser	missense_variant	3/4		NP_067154.1	Q6ISS4-2
LAIR2	XM_011526961.3 linkuse as main transcript	c.118C>T	p.Pro40Ser	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.154C>T	p.Pro52Ser	missense_variant	3/5	1	NM_002288.6	ENSP00000301202.2	Q6ISS4-1
LAIR2	ENST00000351841.2 linkuse as main transcript	c.154C>T	p.Pro52Ser	missense_variant	3/4	1		ENSP00000301203.2	Q6ISS4-2
LAIR2	ENST00000412608.5 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	3/3	1		ENSP00000390729.1	C9JFQ0
LAIR2	ENST00000610651.1 linkuse as main transcript	c.100C>T	p.Pro34Ser	missense_variant	2/2	5		ENSP00000484484.1	A0A087X1V4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 28, 2022

The c.154C>T (p.P52S) alteration is located in exon 3 (coding exon 3) of the LAIR2 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the proline (P) at amino acid position 52 to be replaced by a serine (S). 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

0.66

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

.;.;T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

M_CAP

Benign

0.0016

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L;L

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.7

D;.;D;D

REVEL

Benign

0.051

Sift

Benign

0.39

T;.;T;T

Sift4G

Pathogenic

0.0

D;D;T;T

Polyphen

1.0

D;.;D;D

Vest4

0.10, 0.12

MutPred

0.37

.;.;Gain of catalytic residue at P52 (P = 0.0267);Gain of catalytic residue at P52 (P = 0.0267);

MVP

0.25

MPC

0.80

ClinPred

0.86

GERP RS

-1.5

Varity_R

0.11

gMVP

0.17

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