2-43411699-A-C

Variant names:

• chr2-43411699-A-C
• rs13429458
• NM_022065.5:c.4059-13560T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022065.5(THADA):​c.4059-13560T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,206 control chromosomes in the GnomAD database, including 1,574 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 0.14 (1574 hom., cov: 33)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 64 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.4059-13560T>G		intron_variant	Intron 28 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.4059-13560T>G		intron_variant	Intron 28 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20902 AN: 152088 Hom.: 1556 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.138 AC: 20962 AN: 152206 Hom.: 1574 Cov.: 33 AF XY: 0.140 AC XY: 10443 AN XY: 74414

African (AFR) AF: 0.174 AC: 7225 AN: 41516

American (AMR) AF: 0.0991 AC: 1514 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3466

East Asian (EAS) AF: 0.195 AC: 1013 AN: 5182

South Asian (SAS) AF: 0.172 AC: 829 AN: 4826

European-Finnish (FIN) AF: 0.172 AC: 1826 AN: 10600

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7656 AN: 68028

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.123 Hom.: 5855

Bravo AF: 0.135

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.78
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: rs13429458; hg19: chr2-43638838;