NM_005565.5:c.1452G>C

Variant names:

• chr5-170250757-C-G
• rs754665101
• NM_005565.5:c.1452G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005565.5(LCP2):​c.1452G>C​(p.Leu484Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,180 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 1 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]

C5orf58 (HGNC:37272): (chromosome 5 open reading frame 58)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37373793).

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.1452G>C	p.Leu484Phe	missense	Exon 20 of 21	NP_005556.1	Q13094
	C5orf58	NR_131091.3		n.202-891C>G		intron	N/A
	C5orf58	NR_131092.3		n.118-891C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP2	ENST00000046794.10	TSL:1 MANE Select	c.1452G>C	p.Leu484Phe	missense	Exon 20 of 21	ENSP00000046794.5	Q13094
	C5orf58	ENST00000524171.5	TSL:1	c.95-891C>G		intron	N/A	ENSP00000490552.1	A0A1B0GVU6
	LCP2	ENST00000968849.1		c.1461G>C	p.Leu487Phe	missense	Exon 20 of 21	ENSP00000638908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249192 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461180 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10 AN XY: 726932

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111422

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.013
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.013	D
Sift4G	Benign	0.097	T
Polyphen		0.017	B
Vest4		0.44
MutPred		0.49		Loss of sheet (P = 0.0817)
MVP		0.83
MPC		0.65
ClinPred		0.58	D
GERP RS		3.7
Varity_R		0.17
gMVP		0.42
Mutation Taster		=74/26	polymorphism

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: rs754665101; hg19: chr5-169677761;