2-43484786-A-G

Position:

• chr2-43484786-A-G

Variant summary

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

The NM_022065.5(THADA):​c.3836+448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,812 control chromosomes in the GnomAD database, including 29,846 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 0.61 (29846 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.3836+448T>C		intron_variant		ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.3836+448T>C		intron_variant		1	NM_022065.5	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93071 AN: 151694 Hom.: 29803 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.614 AC: 93172 AN: 151812 Hom.: 29846 Cov.: 31 AF XY: 0.606 AC XY: 44977 AN XY: 74180

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.590

Alfa AF: 0.563 Hom.: 4920

Bravo AF: 0.610

Asia WGS AF: 0.507 AC: 1754 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.93
DANN	Benign	0.66

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: rs6544661; hg19: chr2-43711925;