Variant 7-123662190-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_207163.3(LMOD2):c.604G>A(p.Ala202Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,613,926 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

LMOD2
NM_207163.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006655246).

BP6

Variant 7-123662190-G-A is Benign according to our data. Variant chr7-123662190-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3344794.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMOD2	NM_207163.3 linkuse as main transcript	c.604G>A	p.Ala202Thr	missense_variant	2/3	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.604G>A	p.Ala202Thr	missense_variant	2/3	2	NM_207163.3	ENSP00000411932	P1	Q6P5Q4-1
LMOD2	ENST00000456238.2 linkuse as main transcript	c.274-849G>A		intron_variant		1		ENSP00000398975

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000390

AC:

AN:

248794

Hom.:

AF XY:

0.000326

AC XY:

AN XY:

134966

show subpopulations

Gnomad AFR exome

AF:

0.00472

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00493

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.00148

AC:

225

AN:

152312

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000309

Hom.:

Bravo

AF:

0.00174

ESP6500AA

AF:

0.00344

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000397

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LMOD2-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 15, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.65

M_CAP

Benign

0.054

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.86

D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.030

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

0.87

Polyphen

0.0080

Vest4

0.20

MVP

0.61

MPC

0.087

ClinPred

0.0046

GERP RS

3.3

Varity_R

0.045

gMVP

0.43

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