Genetic Variant LCP2:c.*536C>G (chr5-170248161-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005565.5(LCP2):c.*536C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,260 control chromosomes in the GnomAD database, including 17,066 homozygotes. 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: 𝑓 0.47 ( 17039 hom., cov: 32)

Exomes 𝑓: 0.44 ( 27 hom. )

Consequence

LCP2
NM_005565.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

5 publications found

Variant links:

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 links:

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

C5orf58 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LCP2	NM_005565.5 link	c.*536C>G	3_prime_UTR_variant	Exon 21 of 21	ENST00000046794.10	NP_005556.1	Q13094
LCP2	XM_047417171.1 link	c.*536C>G	3_prime_UTR_variant	Exon 19 of 19		XP_047273127.1
C5orf58	NR_131091.3 link	n.202-3487G>C	intron_variant	Intron 3 of 3
C5orf58	NR_131092.3 link	n.118-3487G>C	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP2	ENST00000046794.10 link	c.*536C>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_005565.5	ENSP00000046794.5		Q13094

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71372

AN:

151854

Hom.:

17028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.441

AC:

127

AN:

288

Hom.:

Cov.:

AF XY:

0.468

AC XY:

AN XY:

190

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.444

AC:

120

AN:

270

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.470

AC:

71411

AN:

151972

Hom.:

17039

Cov.:

AF XY:

0.466

AC XY:

34643

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.403

AC:

16693

AN:

41434

American (AMR)

AF:

0.465

AC:

7107

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1650

AN:

3468

East Asian (EAS)

AF:

0.457

AC:

2367

AN:

5178

South Asian (SAS)

AF:

0.516

AC:

2487

AN:

4822

European-Finnish (FIN)

AF:

0.422

AC:

4449

AN:

10536

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34945

AN:

67938

Other (OTH)

AF:

0.486

AC:

1026

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1973

3946

5919

7892

9865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.353

Hom.:

948

Bravo

AF:

0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.19

(source)

DANN

Benign

0.64

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over