5-170296109-C-T

Variant names:

• chr5-170296109-C-T
• rs182618
• NM_005565.5:c.78+1425G>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.78+1425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,130 control chromosomes in the GnomAD database, including 41,284 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 0.73 (41284 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 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.78+1425G>A		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.78+1425G>A		intron	N/A	ENSP00000046794.5
	LCP2	ENST00000519149.1	TSL:3	n.251+1425G>A		intron	N/A
	LCP2	ENST00000519594.5	TSL:2	n.194+1425G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111543 AN: 152012 Hom.: 41252 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.734 AC: 111626 AN: 152130 Hom.: 41284 Cov.: 32 AF XY: 0.729 AC XY: 54233 AN XY: 74370

African (AFR) AF: 0.833 AC: 34575 AN: 41516

American (AMR) AF: 0.691 AC: 10554 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2674 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2630 AN: 5174

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4826

European-Finnish (FIN) AF: 0.676 AC: 7139 AN: 10556

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 48436 AN: 67996

Other (OTH) AF: 0.740 AC: 1561 AN: 2110

Alfa AF: 0.715 Hom.: 170112

Bravo AF: 0.736

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.23
PhyloP100		0.13
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: rs182618; hg19: chr5-169723113;