19-54574451-A-C

Position:

• chr19-54574451-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000391738.8(LILRA2):​c.221A>C​(p.Gln74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LILRA2 ENST00000391738.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.78

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07938743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LILRA2	NM_001130917.3	c.221A>C	p.Gln74Pro	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	c.221A>C	p.Gln74Pro	missense_variant	3/8	1	NM_001130917.3	ENSP00000375618.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.221A>C (p.Q74P) alteration is located in exon 3 (coding exon 3) of the LILRA2 gene. This alteration results from a A to C substitution at nucleotide position 221, causing the glutamine (Q) at amino acid position 74 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.20
DANN	Benign	0.39
DEOGEN2	Benign	0.0016	T;.;.;.;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.27	T;.;.;.;T;.
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.079	T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PROVEAN	Benign	2.5	N;N;N;N;N;.
REVEL	Benign	0.040
Sift	Benign	0.42	T;T;T;T;T;.
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;B;.
Vest4		0.10, 0.10, 0.13, 0.13, 0.12
MutPred		0.44		Loss of MoRF binding (P = 0.0485);Loss of MoRF binding (P = 0.0485);Loss of MoRF binding (P = 0.0485);Loss of MoRF binding (P = 0.0485);.;Loss of MoRF binding (P = 0.0485);
MVP		0.076
MPC		0.019
ClinPred		0.20	T
GERP RS		-4.8
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55085918;