2-43579779-C-T

Variant names:

• chr2-43579779-C-T
• rs10495903
• NM_022065.5:c.722-1172G>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.722-1172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,048 control chromosomes in the GnomAD database, including 1,297 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 0.13 (1297 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 75 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.722-1172G>A		intron_variant	Intron 8 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.722-1172G>A		intron_variant	Intron 8 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19089 AN: 151930 Hom.: 1296 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.126 AC: 19113 AN: 152048 Hom.: 1297 Cov.: 32 AF XY: 0.121 AC XY: 8965 AN XY: 74330

African (AFR) AF: 0.161 AC: 6682 AN: 41462

American (AMR) AF: 0.0795 AC: 1214 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3470

East Asian (EAS) AF: 0.00580 AC: 30 AN: 5172

South Asian (SAS) AF: 0.149 AC: 716 AN: 4816

European-Finnish (FIN) AF: 0.0726 AC: 768 AN: 10578

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8881 AN: 67964

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.129 Hom.: 4087

Bravo AF: 0.123

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.043
DANN	Benign	0.63
PhyloP100		-2.1
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: rs10495903; hg19: chr2-43806918;