Variant 7-123656226-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207163.3(LMOD2):c.263A>C(p.Glu88Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LMOD2
NM_207163.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

LMOD2 (HGNC:6648): (leiomodin 2) Enables actin monomer binding activity and tropomyosin binding activity. Involved in actin nucleation; positive regulation of actin filament polymerization; and sarcomere organization. Located in actin filament and sarcomere. Colocalizes with M band. [provided by Alliance of Genome Resources, Apr 2022]

LMOD2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10798955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMOD2	NM_207163.3 linkuse as main transcript	c.263A>C	p.Glu88Ala	missense_variant	1/3	ENST00000458573.3	NP_997046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMOD2	ENST00000458573.3 linkuse as main transcript	c.263A>C	p.Glu88Ala	missense_variant	1/3	2	NM_207163.3	ENSP00000411932.2		Q6P5Q4-1
LMOD2	ENST00000456238.2 linkuse as main transcript	c.263A>C	p.Glu88Ala	missense_variant	1/2	1		ENSP00000398975.2		C9J8F4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000420

AC:

AN:

237904

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000581

Gnomad SAS 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:

0.00000206

AC:

AN:

1454150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.263A>C (p.E88A) alteration is located in exon 1 (coding exon 1) of the LMOD2 gene. This alteration results from a A to C substitution at nucleotide position 263, causing the glutamic acid (E) at amino acid position 88 to be replaced by an alanine (A). 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

0.096

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

N;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.056

Sift

Benign

0.35

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0070

B;.

Vest4

0.10

MutPred

0.66

Loss of solvent accessibility (P = 0.002);Loss of solvent accessibility (P = 0.002);

MVP

0.52

MPC

0.098

ClinPred

0.15

GERP RS

5.7

Varity_R

0.13

gMVP

0.058

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