5-170259003-T-A

Variant names:

• chr5-170259003-T-A
• rs432621
• NM_005565.5:c.958-125A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005565.5(LCP2):​c.958-125A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 497,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: LCP2 NM_005565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 0 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: DEFINITIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	NM_005565.5	MANE Select	c.958-125A>T		intron	N/A	NP_005556.1	Q13094

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.958-125A>T		intron	N/A	ENSP00000046794.5	Q13094
	LCP2	ENST00000968849.1		c.967-125A>T		intron	N/A	ENSP00000638908.1
	LCP2	ENST00000968850.1		c.874-125A>T		intron	N/A	ENSP00000638909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000201 AC: 1 AN: 497076 Hom.: 0 AF XY: 0.00000375 AC XY: 1 AN XY: 266884

African (AFR) AF: 0.00 AC: 0 AN: 13406

American (AMR) AF: 0.00 AC: 0 AN: 23302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15578

East Asian (EAS) AF: 0.00 AC: 0 AN: 31138

South Asian (SAS) AF: 0.00 AC: 0 AN: 50056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3188

European-Non Finnish (NFE) AF: 0.00000332 AC: 1 AN: 301604

Other (OTH) AF: 0.00 AC: 0 AN: 27888

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		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

Other links and lift over

dbSNP: rs432621; hg19: chr5-169686007;