2-43391680-C-T

Variant names:

• chr2-43391680-C-T
• rs11899863
• NM_022065.5:c.4227+6291G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.4227+6291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,022 control chromosomes in the GnomAD database, including 558 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 0.082 (558 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 30 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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.4227+6291G>A		intron_variant	Intron 29 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.4227+6291G>A		intron_variant	Intron 29 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12489 AN: 151890 Hom.: 557 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0737

GnomAD4 exome AF: 0.143 AC: 2 AN: 14 Hom.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 2 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0822 AC: 12494 AN: 152008 Hom.: 558 Cov.: 32 AF XY: 0.0767 AC XY: 5699 AN XY: 74298

African (AFR) AF: 0.0901 AC: 3734 AN: 41426

American (AMR) AF: 0.0609 AC: 930 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.0235 AC: 113 AN: 4814

European-Finnish (FIN) AF: 0.0438 AC: 462 AN: 10544

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6620 AN: 67996

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0495 Hom.: 58

Bravo AF: 0.0840

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.8
DANN	Benign	0.89
PhyloP100		-0.25
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: rs11899863; hg19: chr2-43618819;