GeneBe

11-1841014-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003282.4(TNNI2):​c.277-17G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TNNI2
NM_003282.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.716

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • distal arthrogryposis type 2B1
    Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • digitotalar dysmorphism
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Sheldon-hall syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TNNI2NM_003282.4 linkc.277-17G>T intron_variant Intron 6 of 7 ENST00000381911.6 NP_003273.1 P48788-1
TNNI2NM_001145829.2 linkc.277-17G>T intron_variant Intron 6 of 7 NP_001139301.1 P48788-1
TNNI2NM_001145841.2 linkc.277-17G>T intron_variant Intron 4 of 5 NP_001139313.1 P48788-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TNNI2ENST00000381911.6 linkc.277-17G>T intron_variant Intron 6 of 7 2 NM_003282.4 ENSP00000371336.1 P48788-1
TNNI2ENST00000252898.11 linkc.277-17G>T intron_variant Intron 5 of 6 3 ENSP00000252898.7 P48788-1
TNNI2ENST00000381905.3 linkc.277-17G>T intron_variant Intron 4 of 5 3 ENSP00000371330.3 P48788-2
TNNI2ENST00000381906.5 linkc.277-17G>T intron_variant Intron 6 of 7 3 ENSP00000371331.1 P48788-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD2 exomes
AF:
0.00000416
AC:
1
AN:
240304
AF XY:
0.00000758
show subpopulations
Gnomad AFR exome
AF:
0.0000713
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1458592
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
725470
African (AFR)
AF:
0.00
AC:
0
AN:
33404
American (AMR)
AF:
0.00
AC:
0
AN:
44546
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26070
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39608
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86020
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52074
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110984
Other (OTH)
AF:
0.00
AC:
0
AN:
60208
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74434
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41552
American (AMR)
AF:
0.00
AC:
0
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67996
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.4
DANN
Benign
0.88
PhyloP100
-0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Other links and lift over

dbSNP: rs112517111; hg19: chr11-1862244; API