chr2-43550515-T-A

Position:

• chr2-43550515-T-A

Variant summary

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

The NM_022065.5(THADA):​c.2948-1147A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,908 control chromosomes in the GnomAD database, including 8,707 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 0.33 (8707 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.2948-1147A>T		intron_variant		ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.2948-1147A>T		intron_variant		1	NM_022065.5	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50310 AN: 151790 Hom.: 8700 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.331 AC: 50343 AN: 151908 Hom.: 8707 Cov.: 32 AF XY: 0.328 AC XY: 24365 AN XY: 74220

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.312

Alfa AF: 0.303 Hom.: 898

Bravo AF: 0.329

Asia WGS AF: 0.345 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.60

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: rs11903287; hg19: chr2-43777654;