19-54508187-G-A

Position:

• chr19-54508187-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002288.6(LAIR2):​c.364+3G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.46 in 1,608,224 control chromosomes in the GnomAD database, including 173,308 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 0.43 (14437 hom., cov: 30)
  • Exomes 𝑓: 0.46 (158871 hom.)
• Consequence: LAIR2 NM_002288.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=15.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAIR2	NM_002288.6	c.364+3G>A		splice_region_variant, intron_variant		ENST00000301202.7	NP_002279.2
LAIR2	NM_021270.5	c.364+3G>A		splice_region_variant, intron_variant			NP_067154.1
LAIR2	XM_011526961.3	c.328+3G>A		splice_region_variant, intron_variant			XP_011525263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAIR2	ENST00000301202.7	c.364+3G>A		splice_region_variant, intron_variant		1	NM_002288.6	ENSP00000301202.2
LAIR2	ENST00000351841.2	c.364+3G>A		splice_region_variant, intron_variant		1		ENSP00000301203.2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64807 AN: 151794 Hom.: 14433 Cov.: 30

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.464 AC: 675654 AN: 1456314 Hom.: 158871 Cov.: 45 AF XY: 0.467 AC XY: 337927 AN XY: 724140

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.497

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.427 AC: 64840 AN: 151910 Hom.: 14437 Cov.: 30 AF XY: 0.431 AC XY: 31987 AN XY: 74224

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.429

Alfa AF: 0.449 Hom.: 7000

Bravo AF: 0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2277974; hg19: -;