5-170252487-C-G

Variant names:

• chr5-170252487-C-G
• rs895809061
• NM_005565.5:c.1270G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005565.5(LCP2):​c.1270G>C​(p.Val424Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38385627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.1270G>C	p.Val424Leu	missense_variant	Exon 19 of 21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.1039G>C	p.Val347Leu	missense_variant	Exon 17 of 19		XP_047273127.1
C5orf58	NR_131091.3	n.1041C>G		non_coding_transcript_exon_variant	Exon 4 of 4
C5orf58	NR_131092.3	n.957C>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.1270G>C	p.Val424Leu	missense_variant	Exon 19 of 21	1	NM_005565.5	ENSP00000046794.5
C5orf58	ENST00000524171.5	c.*832C>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000490552.1
LCP2	ENST00000521416.5	c.655G>C	p.Val219Leu	missense_variant	Exon 11 of 13	2		ENSP00000428871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000435 AC: 1 AN: 229834 Hom.: 0 AF XY: 0.00000806 AC XY: 1 AN XY: 124088

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420520 Hom.: 0 Cov.: 24 AF XY: 0.00000141 AC XY: 1 AN XY: 707442

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;T;D
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.95	L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Uncertain	0.49
Sift	Benign	0.15	T;.;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.031	B;.;P
Vest4		0.46
MutPred		0.51		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;
MVP		0.87
MPC		0.35
ClinPred		0.44	T
GERP RS		3.2
Varity_R		0.063
gMVP		0.59

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: rs895809061; hg19: chr5-169679491;