5-170296225-C-T

Variant names:

• chr5-170296225-C-T
• rs6866733
• NM_005565.5:c.78+1309G>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+1309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,048 control chromosomes in the GnomAD database, including 3,546 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 0.21 (3546 hom., cov: 32)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 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+1309G>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+1309G>A		intron	N/A	ENSP00000046794.5
	LCP2	ENST00000968849.1		c.78+1309G>A		intron	N/A	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.78+1309G>A		intron	N/A	ENSP00000638909.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31967 AN: 151928 Hom.: 3529 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.211 AC: 32014 AN: 152048 Hom.: 3546 Cov.: 32 AF XY: 0.212 AC XY: 15775 AN XY: 74332

African (AFR) AF: 0.263 AC: 10908 AN: 41454

American (AMR) AF: 0.168 AC: 2563 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1194 AN: 5172

South Asian (SAS) AF: 0.317 AC: 1528 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1918 AN: 10564

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12453 AN: 67964

Other (OTH) AF: 0.195 AC: 413 AN: 2114

Alfa AF: 0.189 Hom.: 3700

Bravo AF: 0.209

Asia WGS AF: 0.260 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.32
PhyloP100		-0.48
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: rs6866733; hg19: chr5-169723229;