Variant 19-54574385-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001130917.3(LILRA2):c.155G>C(p.Ser52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

LILRA2
NM_001130917.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.676

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032972693).

BP6

Variant 19-54574385-G-C is Benign according to our data. Variant chr19-54574385-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2621129.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA2	NM_001130917.3 linkuse as main transcript	c.155G>C	p.Ser52Thr	missense_variant	3/8	ENST00000391738.8	NP_001124389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LILRA2	ENST00000391738.8 linkuse as main transcript	c.155G>C	p.Ser52Thr	missense_variant	3/8	1	NM_001130917.3	ENSP00000375618	P4	Q8N149-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251456

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.071

DANN

Benign

0.48

DEOGEN2

Benign

0.0028

T;.;.;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00051

LIST_S2

Benign

0.38

T;.;.;.;T;.

M_CAP

Benign

0.0011

MetaRNN

Benign

0.033

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PROVEAN

Benign

-0.45

N;N;N;N;N;.

REVEL

Benign

0.011

Sift

Benign

0.83

T;T;T;T;T;.

Sift4G

Benign

0.98

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;B;.

Vest4

0.041, 0.040, 0.080, 0.079, 0.13

MutPred

0.20

Loss of disorder (P = 0.147);Loss of disorder (P = 0.147);Loss of disorder (P = 0.147);Loss of disorder (P = 0.147);.;Loss of disorder (P = 0.147);

MVP

0.081

MPC

0.017

ClinPred

0.13

GERP RS

-3.1

gMVP

0.092

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over