chr2-43525243-T-C

Variant names:

• chr2-43525243-T-C
• rs6708660
• NM_022065.5:c.3374+2636A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.3374+2636A>G		intron_variant	Intron 22 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3374+2636A>G		intron_variant	Intron 22 of 37	1	NM_022065.5	ENSP00000386088.2

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

African (AFR) AF: 0.619 AC: 25636 AN: 41430

American (AMR) AF: 0.292 AC: 4466 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5188

South Asian (SAS) AF: 0.390 AC: 1872 AN: 4806

European-Finnish (FIN) AF: 0.285 AC: 3021 AN: 10594

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26777 AN: 67986

Other (OTH) AF: 0.405 AC: 856 AN: 2114

Alfa AF: 0.392 Hom.: 19838

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
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6708660; hg19: chr2-43752382;