dbSNP rs202049649: LAIR2:p.Thr21Lys (chr19-54503727-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002288.6(LAIR2):c.62C>A(p.Thr21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T21M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LAIR2
NM_002288.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.19092882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR2	NM_002288.6 link	c.62C>A	p.Thr21Lys	missense_variant	Exon 2 of 5	ENST00000301202.7	NP_002279.2	Q6ISS4-1
LAIR2	NM_021270.5 link	c.62C>A	p.Thr21Lys	missense_variant	Exon 2 of 4		NP_067154.1	Q6ISS4-2
LAIR2	XM_011526961.3 link	c.34+775C>A		intron_variant	Intron 1 of 3		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAIR2	ENST00000301202.7 link	c.62C>A	p.Thr21Lys	missense_variant	Exon 2 of 5	1	NM_002288.6	ENSP00000301202.2	Q6ISS4-1
LAIR2	ENST00000351841.2 link	c.62C>A	p.Thr21Lys	missense_variant	Exon 2 of 4	1		ENSP00000301203.2	Q6ISS4-2
LAIR2	ENST00000412608.5 link	c.44C>A	p.Thr15Lys	missense_variant	Exon 2 of 3	1		ENSP00000390729.1	C9JFQ0
LAIR2	ENST00000610651.1 link	c.17-4164C>A		intron_variant	Intron 1 of 1	5		ENSP00000484484.1	A0A087X1V4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.072

.;T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.0016

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

.;L;L

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0030

D;T;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.73

P;B;P

Vest4

0.40, 0.39

MutPred

0.65

.;Gain of methylation at T21 (P = 0.016);Gain of methylation at T21 (P = 0.016);

MVP

0.29

MPC

0.29

ClinPred

0.76

GERP RS

-0.035

Varity_R

0.081

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

Other links and lift over