Variant 19-54587200-G-C 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>C variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,608,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 0 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 9, offset of 9, new splice context is: tctttgtccaccatccctAGgcc. 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 (SAS) allele frequency at 95% confidence interval = 0.0643 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>C	splice_acceptor_variant, intron_variant	ENST00000391738.8	NP_001124389.2	Q8N149-1
LILRA2	NM_001290271.2 linkuse as main transcript	c.*42-1G>C	splice_acceptor_variant, intron_variant		NP_001277200.1
LILRA2	NM_006866.4 linkuse as main transcript	c.1256-1G>C	splice_acceptor_variant, intron_variant		NP_006857.2	Q8N149-2
LILRA2	NM_001290270.1 linkuse as main transcript	c.1220-1G>C	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>C		splice_acceptor_variant, intron_variant		1	NM_001130917.3	ENSP00000375618.3		Q8N149-1

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

543

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00792

Gnomad SAS

AF:

0.0708

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00188

AC:

465

AN:

247804

Hom.:

AF XY:

0.00233

AC XY:

311

AN XY:

133320

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00301

AC:

4385

AN:

1456214

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3085

AN XY:

723718

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00666

Gnomad4 SAS exome

AF:

0.0398

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000483

Gnomad4 OTH exome

AF:

0.00292

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152152

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00814

Gnomad4 SAS

AF:

0.0705

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000225

Hom.:

ExAC

AF:

0.00829

AC:

1006

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.93

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.81

DANN

Benign

0.46

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.00014

GERP RS

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.33

SpliceAI score (max)

0.83

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.83

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