Variant 7-123662248-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_207163.3(LMOD2):c.662T>C(p.Ile221Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00255 in 1,613,922 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 7 hom. )

Consequence

LMOD2
NM_207163.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.26

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.075784504).

BP6

Variant 7-123662248-T-C is Benign according to our data. Variant chr7-123662248-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2499056.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMOD2	NM_207163.3 linkuse as main transcript	c.662T>C	p.Ile221Thr	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.662T>C	p.Ile221Thr	missense_variant	2/3	2	NM_207163.3	ENSP00000411932.2		Q6P5Q4-1
LMOD2	ENST00000456238.2 linkuse as main transcript	c.274-791T>C		intron_variant		1		ENSP00000398975.2		C9J8F4

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00165

AC:

410

AN:

249002

Hom.:

AF XY:

0.00152

AC XY:

205

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00265

AC:

3868

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1830

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00225

Gnomad4 NFE exome

AF:

0.00319

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152226

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00160

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000481

AC:

ESP6500EA

AF:

0.00320

AC:

ExAC

AF:

0.00162

AC:

196

EpiCase

AF:

0.00240

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

LMOD2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.076

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

REVEL

Pathogenic

0.85

Sift

Uncertain

0.017

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.71

MVP

0.88

MPC

0.53

ClinPred

0.052

GERP RS

5.0

Varity_R

0.22

gMVP

0.57

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