19-54508038-A-C

Variant names:

• chr19-54508038-A-C
• NM_002288.6:c.218A>C

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.218A>C​(p.Asn73Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAIR2 NM_002288.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.38
• 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=0.06975499).

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.218A>C	p.Asn73Thr	missense	Exon 3 of 5	NP_002279.2
	LAIR2	NM_021270.5		c.218A>C	p.Asn73Thr	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.218A>C	p.Asn73Thr	missense	Exon 3 of 5	ENSP00000301202.2	Q6ISS4-1
	LAIR2	ENST00000351841.2	TSL:1	c.218A>C	p.Asn73Thr	missense	Exon 3 of 4	ENSP00000301203.2	Q6ISS4-2
	LAIR2	ENST00000412608.5	TSL:1	c.200A>C	p.Asn67Thr	missense	Exon 3 of 3	ENSP00000390729.1	C9JFQ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.010
DANN	Benign	0.22
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.011	N
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.4
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.010
Sift	Benign	0.037	D
Sift4G	Benign	0.28	T
Polyphen		0.47	P
Vest4		0.12
MutPred		0.41		Gain of phosphorylation at N73 (P = 0.0354)
MVP		0.13
MPC		0.23
ClinPred		0.15	T
GERP RS		-6.6
Varity_R		0.11
gMVP		0.064
Mutation Taster		=99/1	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

hg19: chr19-55019253;