2-43327590-G-C

Variant names:

• chr2-43327590-G-C
• rs4128209
• NM_022065.5:c.4344-7050C>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.4344-7050C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,926 control chromosomes in the GnomAD database, including 6,097 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 0.27 (6097 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.4344-7050C>G		intron_variant	Intron 30 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.4344-7050C>G		intron_variant	Intron 30 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40360 AN: 151806 Hom.: 6073 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.266 AC: 40429 AN: 151926 Hom.: 6097 Cov.: 31 AF XY: 0.262 AC XY: 19439 AN XY: 74260

African (AFR) AF: 0.406 AC: 16809 AN: 41388

American (AMR) AF: 0.227 AC: 3465 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3468

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5178

South Asian (SAS) AF: 0.253 AC: 1214 AN: 4804

European-Finnish (FIN) AF: 0.213 AC: 2250 AN: 10560

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15122 AN: 67944

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.101 Hom.: 128

Bravo AF: 0.268

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.53
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: rs4128209; hg19: chr2-43554729;