Variant rs2271441 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003282.4(TNNI2):c.186+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,006 control chromosomes in the GnomAD database, including 34,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2701 hom., cov: 34)

Exomes 𝑓: 0.20 ( 32290 hom. )

Consequence

TNNI2
NM_003282.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.180

Variant links:

Genes affected

TNNI2 (HGNC:11946): (troponin I2, fast skeletal type) This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

TNNI2 links:

TNNI2 (HGNC:):

TNNI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-1840682-G-A is Benign according to our data. Variant chr11-1840682-G-A is described in ClinVar as [Benign]. Clinvar id is 140483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TNNI2	NM_003282.4 linkuse as main transcript	c.186+26G>A	intron_variant	ENST00000381911.6	NP_003273.1	P48788-1
TNNI2	NM_001145829.2 linkuse as main transcript	c.186+26G>A	intron_variant		NP_001139301.1	P48788-1
TNNI2	NM_001145841.2 linkuse as main transcript	c.186+26G>A	intron_variant		NP_001139313.1	P48788-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI2	ENST00000381911.6 linkuse as main transcript	c.186+26G>A		intron_variant		2	NM_003282.4	ENSP00000371336.1		P48788-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26637

AN:

151970

Hom.:

2700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.0535

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.279

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.183

AC:

44897

AN:

245690

Hom.:

4755

AF XY:

0.189

AC XY:

25356

AN XY:

134244

show subpopulations

Gnomad AFR exome

AF:

0.0931

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.0541

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.204

AC:

298500

AN:

1459918

Hom.:

32290

Cov.:

AF XY:

0.206

AC XY:

149755

AN XY:

726252

show subpopulations

Gnomad4 AFR exome

AF:

0.0921

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.0643

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.168

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.175

AC:

26646

AN:

152088

Hom.:

2701

Cov.:

AF XY:

0.172

AC XY:

12813

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.0540

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.218

Hom.:

725

Bravo

AF:

0.169

Asia WGS

AF:

0.108

AC:

376

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	literature only	TNNI2 homepage - Leiden Muscular Dystrophy pages	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Distal arthrogryposis type 2B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.0

DANN

Benign

0.84

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