5-170265550-G-A

Variant names:

• chr5-170265550-G-A
• rs2338872
• NM_005565.5:c.772+1258C>T

Variant summary

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

The NM_005565.5(LCP2):​c.772+1258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,072 control chromosomes in the GnomAD database, including 33,514 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 0.66 (33514 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005565.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	NM_005565.5	MANE Select	c.772+1258C>T		intron	N/A	NP_005556.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.772+1258C>T		intron	N/A	ENSP00000046794.5
	LCP2	ENST00000521416.5	TSL:2	c.157+1258C>T		intron	N/A	ENSP00000428871.1
	LCP2	ENST00000520344.1	TSL:5	c.73+1459C>T		intron	N/A	ENSP00000430391.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99719 AN: 151954 Hom.: 33461 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.656 AC: 99831 AN: 152072 Hom.: 33514 Cov.: 32 AF XY: 0.663 AC XY: 49247 AN XY: 74332

African (AFR) AF: 0.746 AC: 30949 AN: 41472

American (AMR) AF: 0.665 AC: 10166 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1806 AN: 3466

East Asian (EAS) AF: 0.957 AC: 4954 AN: 5178

South Asian (SAS) AF: 0.687 AC: 3312 AN: 4822

European-Finnish (FIN) AF: 0.626 AC: 6609 AN: 10562

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39894 AN: 67970

Other (OTH) AF: 0.629 AC: 1328 AN: 2110

Alfa AF: 0.608 Hom.: 54009

Bravo AF: 0.666

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.018
DANN	Benign	0.60
PhyloP100		-1.6
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: rs2338872; hg19: chr5-169692554;