rs10068619

Variant names:

• chr5-170290735-C-T
• rs10068619
• NM_005565.5:c.141+2575G>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.141+2575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,184 control chromosomes in the GnomAD database, including 1,072 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 0.11 (1072 hom., cov: 31)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.141+2575G>A		intron_variant	Intron 2 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.141+2575G>A		intron_variant	Intron 2 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.141+2575G>A		intron_variant	Intron 2 of 20	1	NM_005565.5	ENSP00000046794.5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17425 AN: 152066 Hom.: 1072 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.115 AC: 17426 AN: 152184 Hom.: 1072 Cov.: 31 AF XY: 0.113 AC XY: 8400 AN XY: 74420

African (AFR) AF: 0.106 AC: 4408 AN: 41502

American (AMR) AF: 0.105 AC: 1601 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5182

South Asian (SAS) AF: 0.104 AC: 499 AN: 4820

European-Finnish (FIN) AF: 0.0902 AC: 957 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9003 AN: 67994

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.124 Hom.: 1742

Bravo AF: 0.113

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.68
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10068619; hg19: chr5-169717739;