5-170296225-C-T

Variant names:

• chr5-170296225-C-T
• rs6866733
• NM_005565.5:c.78+1309G>A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.78+1309G>A		intron_variant	Intron 1 of 20	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.78+1309G>A		intron_variant	Intron 1 of 18		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.78+1309G>A		intron_variant	Intron 1 of 20	1	NM_005565.5	ENSP00000046794.5

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

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.195

Alfa AF: 0.187 Hom.: 2783

Bravo AF: 0.209

Asia WGS AF: 0.260 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs6866733; hg19: chr5-169723229;