Variant 2-43231151-TGAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_022065.5(THADA):c.5656_5658delTTC(p.Phe1886del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,918 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

THADA
NM_022065.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

THADA (HGNC:19217): (THADA armadillo repeat containing) This gene is the target of 2p21 choromosomal aberrations in benign thyroid adenomas. Single nucleotide polymorphisms (SNPs) in this gene may be associated with type 2 diabetes and polycystic ovary syndrome. The encoded protein is likely involved in the death receptor pathway and apoptosis. [provided by RefSeq, Sep 2016]

THADA links:

THADA (HGNC:):

THADA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_022065.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-43231151-TGAA-T is Benign according to our data. Variant chr2-43231151-TGAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650853.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5 linkuse as main transcript	c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	38/38	ENST00000405975.7	NP_071348.3	Q6YHU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7 linkuse as main transcript	c.5656_5658delTTC	p.Phe1886del	conservative_inframe_deletion	38/38	1	NM_022065.5	ENSP00000386088.2		Q6YHU6-1

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

345

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00266

AC:

661

AN:

248924

Hom.:

AF XY:

0.00258

AC XY:

349

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.00259

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00269

AC:

3937

AN:

1461622

Hom.:

AF XY:

0.00256

AC XY:

1859

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.00278

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00227

AC:

345

AN:

152296

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.00223

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00122

EpiCase

AF:

0.00207

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

Feb 01, 2023

THADA: BS2 -

THADA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2020

This variant is classified as 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

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