rs2271442

Variant names:

• chr11-1840938-C-T
• rs2271442
• NM_003282.4:c.276+30C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1840938-C-T
• chr11-1840938-C-A
• chr11-1840938-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003282.4(TNNI2):​c.276+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,602,912 control chromosomes in the GnomAD database, including 52,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3859 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48784 hom.)
• Consequence: TNNI2 NM_003282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.109
• Publications: 7 publications found

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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sheldon-hall syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-1840938-C-T is Benign according to our data. Variant chr11-1840938-C-T is described in ClinVar as Benign. ClinVar VariationId is 259023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI2	NM_003282.4	MANE Select	c.276+30C>T		intron	N/A	NP_003273.1	P48788-1
	TNNI2	NM_001145829.2		c.276+30C>T		intron	N/A	NP_001139301.1	P48788-1
	TNNI2	NM_001145841.2		c.276+30C>T		intron	N/A	NP_001139313.1	P48788-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNNI2	ENST00000381911.6	TSL:2 MANE Select	c.276+30C>T		intron	N/A	ENSP00000371336.1	P48788-1
	TNNI2	ENST00000252898.11	TSL:3	c.276+30C>T		intron	N/A	ENSP00000252898.7	P48788-1
	TNNI2	ENST00000381905.3	TSL:3	c.276+30C>T		intron	N/A	ENSP00000371330.3	P48788-2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32116 AN: 151862 Hom.: 3857 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.248 AC: 56394 AN: 227494 AF XY: 0.252

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.260

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.255 AC: 370100 AN: 1450936 Hom.: 48784 Cov.: 37 AF XY: 0.256 AC XY: 184262 AN XY: 721096

African (AFR) AF: 0.101 AC: 3369 AN: 33212

American (AMR) AF: 0.189 AC: 8232 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4399 AN: 25882

East Asian (EAS) AF: 0.242 AC: 9443 AN: 39058

South Asian (SAS) AF: 0.256 AC: 21906 AN: 85418

European-Finnish (FIN) AF: 0.348 AC: 17897 AN: 51424

Middle Eastern (MID) AF: 0.151 AC: 863 AN: 5700

European-Non Finnish (NFE) AF: 0.262 AC: 290103 AN: 1106952

Other (OTH) AF: 0.232 AC: 13888 AN: 59840

GnomAD4 genome AF: 0.211 AC: 32119 AN: 151976 Hom.: 3859 Cov.: 33 AF XY: 0.217 AC XY: 16125 AN XY: 74294

African (AFR) AF: 0.108 AC: 4485 AN: 41486

American (AMR) AF: 0.179 AC: 2737 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1221 AN: 5134

South Asian (SAS) AF: 0.249 AC: 1198 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10574

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17382 AN: 67906

Other (OTH) AF: 0.169 AC: 357 AN: 2116

Alfa AF: 0.179 Hom.: 644

Bravo AF: 0.193

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.96
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2271442; hg19: chr11-1862168;