rs572192

Variant names:

• chr5-170261593-C-T
• rs572192
• NM_005565.5:c.927-456G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005565.5(LCP2):​c.927-456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,094 control chromosomes in the GnomAD database, including 33,749 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 0.65 (33749 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 5 publications found

Genes affected

LCP2 (HGNC:6529): (lymphocyte cytosolic protein 2) This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability. [provided by RefSeq, Nov 2016]

LCP2 Gene-Disease associations (from GenCC):

• immunodeficiency 81

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.927-456G>A		intron_variant	Intron 13 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.696-456G>A		intron_variant	Intron 11 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.927-456G>A		intron_variant	Intron 13 of 20	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.312-456G>A		intron_variant	Intron 5 of 12	2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.228-456G>A		intron_variant	Intron 4 of 7	5		ENSP00000430391.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98554 AN: 151976 Hom.: 33688 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.615

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98669 AN: 152094 Hom.: 33749 Cov.: 32 AF XY: 0.649 AC XY: 48253 AN XY: 74346

African (AFR) AF: 0.888 AC: 36865 AN: 41534

American (AMR) AF: 0.595 AC: 9096 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3468

East Asian (EAS) AF: 0.549 AC: 2836 AN: 5164

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4828

European-Finnish (FIN) AF: 0.622 AC: 6566 AN: 10554

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36913 AN: 67936

Other (OTH) AF: 0.608 AC: 1286 AN: 2114

Alfa AF: 0.470 Hom.: 1666

Bravo AF: 0.658

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.57
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs572192; hg19: chr5-169688597;