19-54507974-C-A

Variant names:

• chr19-54507974-C-A
• rs2085394862
• NM_002288.6:c.154C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002288.6(LAIR2):​c.154C>A​(p.Pro52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. P52L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAIR2 NM_002288.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1218591).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002288.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR2	NM_002288.6	MANE Select	c.154C>A	p.Pro52Thr	missense	Exon 3 of 5	NP_002279.2
	LAIR2	NM_021270.5		c.154C>A	p.Pro52Thr	missense	Exon 3 of 4	NP_067154.1	Q6ISS4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR2	ENST00000301202.7	TSL:1 MANE Select	c.154C>A	p.Pro52Thr	missense	Exon 3 of 5	ENSP00000301202.2	Q6ISS4-1
	LAIR2	ENST00000351841.2	TSL:1	c.154C>A	p.Pro52Thr	missense	Exon 3 of 4	ENSP00000301203.2	Q6ISS4-2
	LAIR2	ENST00000412608.5	TSL:1	c.136C>A	p.Pro46Thr	missense	Exon 3 of 3	ENSP00000390729.1	C9JFQ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.034	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.83
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.061
Sift	Benign	0.33	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.34		Gain of MoRF binding (P = 0.0615)
MVP		0.28
MPC		0.86
ClinPred		0.83	D
GERP RS		-1.5
Varity_R		0.11
gMVP		0.19
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2085394862; hg19: chr19-55019189;