19-54502872-C-T

Variant names:

• chr19-54502872-C-T
• rs2042287
• NM_002288.6:c.-47C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002288.6(LAIR2):​c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,612,690 control chromosomes in the GnomAD database, including 12,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1299 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11406 hom.)
• Consequence: LAIR2 NM_002288.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR2	NM_002288.6	c.-47C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000301202.7	NP_002279.2
LAIR2	NM_021270.5	c.-47C>T		5_prime_UTR_variant	Exon 1 of 4		NP_067154.1
LAIR2	XM_011526961.3	c.-47C>T		5_prime_UTR_variant	Exon 1 of 4		XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAIR2	ENST00000301202.7	c.-47C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_002288.6	ENSP00000301202.2
LAIR2	ENST00000412608.5	c.17-828C>T		intron_variant	Intron 1 of 2	1		ENSP00000390729.1
LAIR2	ENST00000610651.1	c.16+4615C>T		intron_variant	Intron 1 of 1	5		ENSP00000484484.1
LAIR2	ENST00000351841.2	c.-47C>T		upstream_gene_variant		1		ENSP00000301203.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19010 AN: 152148 Hom.: 1293 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.142 AC: 35529 AN: 250994 AF XY: 0.139

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.0979

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.0917

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.117 AC: 170541 AN: 1460424 Hom.: 11406 Cov.: 33 AF XY: 0.118 AC XY: 86065 AN XY: 726650

African (AFR) AF: 0.140 AC: 4697 AN: 33450

American (AMR) AF: 0.267 AC: 11946 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2622 AN: 26126

East Asian (EAS) AF: 0.100 AC: 3982 AN: 39684

South Asian (SAS) AF: 0.201 AC: 17293 AN: 86194

European-Finnish (FIN) AF: 0.0945 AC: 5047 AN: 53406

Middle Eastern (MID) AF: 0.106 AC: 614 AN: 5768

European-Non Finnish (NFE) AF: 0.105 AC: 116897 AN: 1110778

Other (OTH) AF: 0.123 AC: 7443 AN: 60336

GnomAD4 genome AF: 0.125 AC: 19043 AN: 152266 Hom.: 1299 Cov.: 32 AF XY: 0.126 AC XY: 9390 AN XY: 74436

African (AFR) AF: 0.142 AC: 5880 AN: 41548

American (AMR) AF: 0.172 AC: 2630 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3466

East Asian (EAS) AF: 0.119 AC: 618 AN: 5174

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4822

European-Finnish (FIN) AF: 0.0982 AC: 1042 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7071 AN: 68028

Other (OTH) AF: 0.143 AC: 303 AN: 2116

Alfa AF: 0.118 Hom.: 523

Bravo AF: 0.135

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.44
PhyloP100		-0.11
PromoterAI		-0.17	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs2042287; hg19: chr19-55014088; COSMIC: COSV56621599; COSMIC: COSV56621599;