Variant X-115165928-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020871.4(LRCH2):c.1111C>G(p.Leu371Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,160,149 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000076 ( 0 hom. 23 hem. )

Consequence

LRCH2
NM_020871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

Variant links:

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]

LRCH2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34411484).

BS2

High Hemizygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH2	NM_020871.4 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/21	ENST00000317135.13	NP_065922.3	Q5VUJ6-1
LRCH2	NM_001243963.2 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/20		NP_001230892.1	Q5VUJ6-2
LRCH2	XM_006724724.4 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/21		XP_006724787.2
LRCH2	XM_017029696.3 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/16		XP_016885185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH2	ENST00000317135.13 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/21	1	NM_020871.4	ENSP00000325091.8		Q5VUJ6-1
LRCH2	ENST00000538422.2 linkuse as main transcript	c.1111C>G	p.Leu371Val	missense_variant	8/20	1		ENSP00000439366.1		Q5VUJ6-2

Frequencies

GnomAD3 genomes

AF:

0.00000903

AC:

AN:

110783

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33253

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000849

AC:

AN:

117806

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37484

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000762

AC:

AN:

1049366

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

337928

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000957

Gnomad4 OTH exome

AF:

0.0000451

GnomAD4 genome

AF:

0.00000903

AC:

AN:

110783

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33253

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.1111C>G (p.L371V) alteration is located in exon 8 (coding exon 8) of the LRCH2 gene. This alteration results from a C to G substitution at nucleotide position 1111, causing the leucine (L) at amino acid position 371 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.34

T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.97

D;.

Vest4

0.46

MutPred

0.25

Gain of glycosylation at T368 (P = 0.1405);Gain of glycosylation at T368 (P = 0.1405);

MVP

0.51

MPC

1.3

ClinPred

0.93

GERP RS

5.7

Varity_R

0.75

gMVP

0.24

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