19-54508038-A-C

Position:

• chr19-54508038-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

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=0.06975499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAIR2	NM_002288.6	c.218A>C	p.Asn73Thr	missense_variant	3/5	ENST00000301202.7	NP_002279.2
LAIR2	NM_021270.5	c.218A>C	p.Asn73Thr	missense_variant	3/4		NP_067154.1
LAIR2	XM_011526961.3	c.182A>C	p.Asn61Thr	missense_variant	2/4		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAIR2	ENST00000301202.7	c.218A>C	p.Asn73Thr	missense_variant	3/5	1	NM_002288.6	ENSP00000301202.2
LAIR2	ENST00000351841.2	c.218A>C	p.Asn73Thr	missense_variant	3/4	1		ENSP00000301203.2
LAIR2	ENST00000412608.5	c.200A>C	p.Asn67Thr	missense_variant	3/3	1		ENSP00000390729.1
LAIR2	ENST00000610651.1	c.164A>C	p.Asn55Thr	missense_variant	2/2	5		ENSP00000484484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.218A>C (p.N73T) alteration is located in exon 3 (coding exon 3) of the LAIR2 gene. This alteration results from a A to C substitution at nucleotide position 218, causing the asparagine (N) at amino acid position 73 to be replaced by a threonine (T). 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	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;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;.;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.4	N;.;N;N
REVEL	Benign	0.010
Sift	Benign	0.037	D;.;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.47	P;.;B;P
Vest4		0.12, 0.15
MutPred		0.41		.;.;Gain of phosphorylation at N73 (P = 0.0354);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55019253;