5-170263243-T-C

Variant names:

• chr5-170263243-T-C
• rs10475933
• NM_005565.5:c.773-251A>G

Variant summary

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

The NM_005565.5(LCP2):​c.773-251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,164 control chromosomes in the GnomAD database, including 39,163 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 0.72 (39163 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 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.773-251A>G		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.773-251A>G		intron	N/A	ENSP00000046794.5
	LCP2	ENST00000521416.5	TSL:2	c.158-251A>G		intron	N/A	ENSP00000428871.1
	LCP2	ENST00000520344.1	TSL:5	c.74-251A>G		intron	N/A	ENSP00000430391.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108789 AN: 152044 Hom.: 39127 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.716 AC: 108881 AN: 152164 Hom.: 39163 Cov.: 32 AF XY: 0.719 AC XY: 53506 AN XY: 74388

African (AFR) AF: 0.702 AC: 29165 AN: 41524

American (AMR) AF: 0.716 AC: 10948 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2397 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4645 AN: 5174

South Asian (SAS) AF: 0.826 AC: 3978 AN: 4814

European-Finnish (FIN) AF: 0.721 AC: 7632 AN: 10578

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47713 AN: 67986

Other (OTH) AF: 0.697 AC: 1470 AN: 2110

Alfa AF: 0.706 Hom.: 65390

Bravo AF: 0.714

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.50
PhyloP100		-0.54
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: rs10475933; hg19: chr5-169690247;