Genetic Variant LAIR2:c.364+3G>A (chr19-54508187-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

Publications

12 publications found

Variant links:

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]

LAIR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.364+3G>A		splice_region intron	N/A	NP_002279.2
	LAIR2	NM_021270.5		c.364+3G>A		splice_region intron	N/A	NP_067154.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LAIR2	ENST00000301202.7	TSL:1 MANE Select	c.364+3G>A	splice_region intron	N/A	ENSP00000301202.2
LAIR2	ENST00000351841.2	TSL:1	c.364+3G>A	splice_region intron	N/A	ENSP00000301203.2
LAIR2	ENST00000956664.1		c.328+3G>A	splice_region intron	N/A	ENSP00000626723.1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64807

AN:

151794

Hom.:

14433

Cov.:

show subpopulations

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.:

AF XY:

0.467

AC XY:

337927

AN XY:

724140

show subpopulations

African (AFR)

AF:

0.316

AC:

10564

AN:

33378

American (AMR)

AF:

0.442

AC:

19695

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

12788

AN:

25750

East Asian (EAS)

AF:

0.247

AC:

9799

AN:

39656

South Asian (SAS)

AF:

0.525

AC:

45096

AN:

85840

European-Finnish (FIN)

AF:

0.569

AC:

30299

AN:

53218

Middle Eastern (MID)

AF:

0.480

AC:

2227

AN:

4638

European-Non Finnish (NFE)

AF:

0.467

AC:

518362

AN:

1109224

Other (OTH)

AF:

0.447

AC:

26824

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

19976

39953

59929

79906

99882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15366

30732

46098

61464

76830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

64840

AN:

151910

Hom.:

14437

Cov.:

AF XY:

0.431

AC XY:

31987

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.321

AC:

13290

AN:

41436

American (AMR)

AF:

0.438

AC:

6681

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1701

AN:

3468

East Asian (EAS)

AF:

0.242

AC:

1250

AN:

5168

South Asian (SAS)

AF:

0.517

AC:

2485

AN:

4810

European-Finnish (FIN)

AF:

0.573

AC:

6039

AN:

10534

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.468

AC:

31789

AN:

67924

Other (OTH)

AF:

0.429

AC:

905

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1845

3689

5534

7378

9223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.445

Hom.:

7323

Bravo

AF:

0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

(source)

PhyloP100

3.9

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over