Variant 11-540736-GTCC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBS1_Supporting

The NM_198075.4(LRRC56):c.53_55delTCC(p.Val18_Arg19delinsGly) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000311 in 1,612,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

LRRC56
NM_198075.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

LRRC56 (HGNC:25430): (leucine rich repeat containing 56) Predicted to be involved in cell projection organization. Predicted to be located in cilium. Implicated in primary ciliary dyskinesia 39. [provided by Alliance of Genome Resources, Apr 2022]

LRRC56 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_198075.4. Strenght limited to Supporting due to length of the change: 1aa.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00021 (32/152186) while in subpopulation AMR AF= 0.000785 (12/15282). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC56	NM_198075.4 linkuse as main transcript	c.53_55delTCC	p.Val18_Arg19delinsGly	disruptive_inframe_deletion	4/14	ENST00000270115.8	NP_932341.1	Q8IYG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC56	ENST00000270115.8 linkuse as main transcript	c.53_55delTCC	p.Val18_Arg19delinsGly	disruptive_inframe_deletion	4/14	1	NM_198075.4	ENSP00000270115.7		Q8IYG6

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000214

AC:

AN:

247118

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

134014

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000375

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000322

AC:

470

AN:

1460010

Hom.:

AF XY:

0.000310

AC XY:

225

AN XY:

726194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000401

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000210

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000302

EpiCase

AF:

0.000545

EpiControl

AF:

0.000713

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ciliary dyskinesia, primary, 39

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetics and Molecular Pathology, SA Pathology

Jun 02, 2023

The LRRC56 c.53_55del variant is classified as a VUS (PM4) The LRRC56 c.53_55del variant results in an inframe deletion in exon 4/14. It is predicted to alter the length of the protein produced by this gene due to an inframe deletion variant in a nonrepeat region (PM4). The variant is rare in population databases (gnomAD allele frequency = 0.021%; 32 het and 0 hom in 152,186 sequenced alleles). The variant has been reported in dbSNP (rs759014538) and has been reported as Uncertain significance by other diagnostic laboratories (ClinVar Variation ID: 1523693). It has not been reported in HGMD (2023.1) or the scientific literature to date. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 15, 2022

This variant, c.53_55del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the LRRC56 protein (p.Val18_Arg19delinsGly). This variant is present in population databases (rs759014538, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LRRC56-related conditions. ClinVar contains an entry for this variant (Variation ID: 1523693). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over