5-170261136-G-C

Variant names:

• chr5-170261136-G-C
• NM_005565.5:c.928C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005565.5(LCP2):​c.928C>G​(p.His310Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000069 in 1,449,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LCP2 NM_005565.5 missense, splice_region
• Scores: Splicing: ADA: 0.005103
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2512884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.928C>G	p.His310Asp	missense_variant, splice_region_variant	Exon 14 of 21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.697C>G	p.His233Asp	missense_variant, splice_region_variant	Exon 12 of 19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.928C>G	p.His310Asp	missense_variant, splice_region_variant	Exon 14 of 21	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.313C>G	p.His105Asp	missense_variant, splice_region_variant	Exon 6 of 13	2		ENSP00000428871.1
LCP2	ENST00000520344.1	c.229C>G	p.His77Asp	missense_variant, splice_region_variant	Exon 5 of 8	5		ENSP00000430391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449484 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 721882

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D;T;T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N;.;N;D
REVEL	Benign	0.13
Sift	Benign	0.087	T;.;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.12	B;.;B;.
Vest4		0.56
MutPred		0.23		Gain of ubiquitination at K309 (P = 0.0231);Gain of ubiquitination at K309 (P = 0.0231);.;.;
MVP		0.61
MPC		0.38
ClinPred		0.46	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0051
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-169688140;