rs782142083

Variant names:

• chrX-115149858-C-T
• rs782142083
• NM_020871.4:c.1664G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-115149858-C-T
• chrX-115149858-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020871.4(LRCH2):​c.1664G>A​(p.Arg555Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,084,640 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R555W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000012 (0 hom. 6 hem.)
• Consequence: LRCH2 NM_020871.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46
• Publications: 2 publications found

Genes affected

LRCH2 (HGNC:29292): (leucine rich repeats and calponin homology domain containing 2) This gene encodes a member of the leucine-rich repeat and calponin homology domain-containing protein family. These family members contain multiple N-terminal leucine-rich repeats, in addition to a C-terminal calponin homology domain, a type of domain that mediates interactions with actin filaments. These proteins are conserved across animal species, and studies of a similar Drosophila protein indicate a function as a cytoskeletal scaffolding protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12859017).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH2	NM_020871.4	MANE Select	c.1664G>A	p.Arg555Gln	missense	Exon 14 of 21	NP_065922.3
	LRCH2	NM_001243963.2		c.1664G>A	p.Arg555Gln	missense	Exon 14 of 20	NP_001230892.1	Q5VUJ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH2	ENST00000317135.13	TSL:1 MANE Select	c.1664G>A	p.Arg555Gln	missense	Exon 14 of 21	ENSP00000325091.8	Q5VUJ6-1
	LRCH2	ENST00000538422.2	TSL:1	c.1664G>A	p.Arg555Gln	missense	Exon 14 of 20	ENSP00000439366.1	Q5VUJ6-2
	LRCH2	ENST00000857824.1		c.1643G>A	p.Arg548Gln	missense	Exon 14 of 21	ENSP00000527883.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000570 AC: 1 AN: 175332 AF XY: 0.0000161

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000120 AC: 13 AN: 1084640 Hom.: 0 Cov.: 27 AF XY: 0.0000170 AC XY: 6 AN XY: 352244

African (AFR) AF: 0.0000383 AC: 1 AN: 26094

American (AMR) AF: 0.00 AC: 0 AN: 34506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19173

East Asian (EAS) AF: 0.00 AC: 0 AN: 29971

South Asian (SAS) AF: 0.0000379 AC: 2 AN: 52789

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.0000120 AC: 10 AN: 832165

Other (OTH) AF: 0.00 AC: 0 AN: 45532

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	0.016	D
MutationAssessor	Benign	1.0	L
PhyloP100		3.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.062
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		0.99	D
Vest4		0.077
MutPred		0.23		Loss of MoRF binding (P = 0.0707)
MVP		0.51
MPC		1.2
ClinPred		0.66	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.31
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782142083; hg19: chrX-114384421; COSMIC: COSV57756804;