Variant rs2241524 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The NM_001130917.3(LILRA2):c.1307-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,466 control chromosomes in the GnomAD database, including 3,515 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 403 hom., cov: 32)

Exomes 𝑓: 0.025 ( 3112 hom. )

Consequence

LILRA2
NM_001130917.3 splice_acceptor, intron

Scores

Splicing: ADA: 0.9973

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.64

Variant links:

Genes affected

LILRA2 (HGNC:6603): (leukocyte immunoglobulin like receptor A2) This gene encodes a member of a family of immunoreceptors that are expressed predominantly on monocytes and B cells, and at lower levels on dendritic cells and natural killer cells. The encoded protein is an activating receptor that inhibits dendritic cell differentiation and antigen presentation and suppresses innate immune response. Alternatively spliced transcript variants encoding different isoforms have been found. This gene is located in a cluster of related genes on chromosome 19 and there is a pseudogene for this gene on chromosome 3. [provided by RefSeq, Mar 2014]

LILRA2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 2.1253443 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.5, offset of 9, new splice context is: tctttgtccaacatccctAGgcc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LILRA2	NM_001130917.3 linkuse as main transcript	c.1307-1G>A	splice_acceptor_variant, intron_variant	ENST00000391738.8	NP_001124389.2	Q8N149-1
LILRA2	NM_001290271.2 linkuse as main transcript	c.*42-1G>A	splice_acceptor_variant, intron_variant		NP_001277200.1
LILRA2	NM_006866.4 linkuse as main transcript	c.1256-1G>A	splice_acceptor_variant, intron_variant		NP_006857.2	Q8N149-2
LILRA2	NM_001290270.1 linkuse as main transcript	c.1220-1G>A	splice_acceptor_variant, intron_variant		NP_001277199.1	A8MZH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA2	ENST00000391738.8 linkuse as main transcript	c.1307-1G>A		splice_acceptor_variant, intron_variant		1	NM_001130917.3	ENSP00000375618.3		Q8N149-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5609

AN:

152048

Hom.:

404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.0488

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.0345

GnomAD3 exomes

AF:

0.0662

AC:

16402

AN:

247804

Hom.:

1795

AF XY:

0.0579

AC XY:

7714

AN XY:

133320

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.0431

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.00965

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0248

AC:

36177

AN:

1461300

Hom.:

3112

Cov.:

AF XY:

0.0243

AC XY:

17630

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.299

Gnomad4 SAS exome

AF:

0.0377

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.00711

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.0370

AC:

5623

AN:

152166

Hom.:

403

Cov.:

AF XY:

0.0403

AC XY:

3001

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0294

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.0486

Gnomad4 FIN

AF:

0.0182

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0487

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.0334

AC:

147

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.0576

AC:

6994

EpiCase

AF:

0.00889

EpiControl

AF:

0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.99

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.1

DANN

Benign

0.50

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0023

GERP RS

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.35

SpliceAI score (max)

0.80

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.80

Position offset: 10

DS_AL_spliceai

0.76

Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over