5-170253135-G-C

Variant names:

• chr5-170253135-G-C
• rs34192428
• NM_005565.5:c.1229C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005565.5(LCP2):​c.1229C>G​(p.Ser410Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,609,648 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., cov: 33)
  • Exomes 𝑓: 0.017 (245 hom.)
• Consequence: LCP2 NM_005565.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049465597).
• BP6: Variant 5-170253135-G-C is Benign according to our data. Variant chr5-170253135-G-C is described in ClinVar as [Benign]. Clinvar id is 2656067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1775/152284) while in subpopulation NFE AF= 0.0176 (1200/68022). AF 95% confidence interval is 0.0168. There are 18 homozygotes in gnomad4. There are 806 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5	c.1229C>G	p.Ser410Cys	missense_variant	Exon 18 of 21	ENST00000046794.10	NP_005556.1
LCP2	XM_047417171.1	c.998C>G	p.Ser333Cys	missense_variant	Exon 16 of 19		XP_047273127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10	c.1229C>G	p.Ser410Cys	missense_variant	Exon 18 of 21	1	NM_005565.5	ENSP00000046794.5
LCP2	ENST00000521416.5	c.614C>G	p.Ser205Cys	missense_variant	Exon 10 of 13	2		ENSP00000428871.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1775 AN: 152166 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00913

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0122 AC: 2980 AN: 244384 Hom.: 24 AF XY: 0.0122 AC XY: 1619 AN XY: 132346

Gnomad AFR exome AF: 0.00362

Gnomad AMR exome AF: 0.00796

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00930

Gnomad FIN exome AF: 0.0129

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0167 AC: 24363 AN: 1457364 Hom.: 245 Cov.: 29 AF XY: 0.0165 AC XY: 11936 AN XY: 724726

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00930

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00916

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0117 AC: 1775 AN: 152284 Hom.: 18 Cov.: 33 AF XY: 0.0108 AC XY: 806 AN XY: 74458

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00914

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0161 Hom.: 17

Bravo AF: 0.0112

TwinsUK AF: 0.0216 AC: 80

ALSPAC AF: 0.0202 AC: 78

ESP6500AA AF: 0.00385 AC: 14

ESP6500EA AF: 0.0201 AC: 164

ExAC AF: 0.0118 AC: 1422

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LCP2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.58	T;T;T
MetaRNN	Benign	0.0049	T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N;.;N
REVEL	Benign	0.19
Sift	Uncertain	0.010	D;.;D
Sift4G	Benign	0.069	T;D;D
Polyphen		1.0	D;.;D
Vest4		0.16
MPC		0.38
ClinPred		0.014	T
GERP RS		3.5
Varity_R		0.049
gMVP		0.45

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: rs34192428; hg19: chr5-169680139;