rs6708660

chr2-43525243-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):c.3374+2636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,082 control chromosomes in the GnomAD database, including 15,322 homozygotes. 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 0.42 (15322 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.3374+2636A>G		intron_variant		ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.3374+2636A>G		intron_variant		1	NM_022065.5	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64538 AN: 151964 Hom.: 15291 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64615 AN: 152082 Hom.: 15322 Cov.: 32 AF XY: 0.414 AC XY: 30798 AN XY: 74350

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.405

Alfa AF: 0.392 Hom.: 15636

Bravo AF: 0.429

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.14
Dann	Benign	0.31

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: rs6708660; hg19: chr2-43752382;