Variant X-115130162-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000317135.13(LRCH2):c.1733A>T(p.Asn578Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 919,477 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000044 ( 0 hom. 2 hem. )

Consequence

LRCH2
ENST00000317135.13 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12824059).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRCH2	NM_020871.4 linkuse as main transcript	c.1733A>T	p.Asn578Ile	missense_variant	15/21	ENST00000317135.13	NP_065922.3
LRCH2	NM_001243963.2 linkuse as main transcript	c.1733A>T	p.Asn578Ile	missense_variant	15/20		NP_001230892.1
LRCH2	XM_006724724.4 linkuse as main transcript	c.1712A>T	p.Asn571Ile	missense_variant	15/21		XP_006724787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH2	ENST00000317135.13 linkuse as main transcript	c.1733A>T	p.Asn578Ile	missense_variant	15/21	1	NM_020871.4	ENSP00000325091	P2	Q5VUJ6-1
LRCH2	ENST00000538422.2 linkuse as main transcript	c.1733A>T	p.Asn578Ile	missense_variant	15/20	1		ENSP00000439366	A2	Q5VUJ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000435

AC:

AN:

919477

Hom.:

Cov.:

AF XY:

0.00000763

AC XY:

AN XY:

261985

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:

0.00000568

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 28, 2023

The c.1733A>T (p.N578I) alteration is located in exon 15 (coding exon 15) of the LRCH2 gene. This alteration results from a A to T substitution at nucleotide position 1733, causing the asparagine (N) at amino acid position 578 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.068

Sift

Benign

0.042

D;T

Sift4G

Benign

0.50

T;T

Polyphen

0.84

P;.

Vest4

0.33

MutPred

0.25

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);

MVP

0.46

MPC

0.89

ClinPred

0.53

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over