2-43231151-TGAA-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PM4_Supporting BP6_Very_Strong BS2

The NM_022065.5(THADA):c.5656_5658del(p.Phe1886del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.24

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 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_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.5656_5658del	p.Phe1886del	inframe_deletion	38/38	ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.5656_5658del	p.Phe1886del	inframe_deletion	38/38	1	NM_022065.5	P1
	ENST00000423354.1	n.44+1539_44+1541del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152178 Hom.: 2 Cov.: 32

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.: 5 AF XY: 0.00258 AC XY: 349 AN XY: 135072

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.: 11 AF XY: 0.00256 AC XY: 1859 AN XY: 727080

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.: 2 Cov.: 32 AF XY: 0.00277 AC XY: 206 AN XY: 74458

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.: 0

Bravo AF: 0.00122

EpiCase AF: 0.00207

EpiControl AF: 0.00249

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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, criteria provided, single submitter

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

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

Other links and lift over

dbSNP: rs544375407; hg19: chr2-43458290;