chr2-43534160-A-G

Position:

• chr2-43534160-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405975.7(THADA):​c.3265-6172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,228 control chromosomes in the GnomAD database, including 1,167 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 0.11 (1167 hom., cov: 32)
• Consequence: THADA ENST00000405975.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5	c.3265-6172T>C		intron_variant		ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3265-6172T>C		intron_variant		1	NM_022065.5	ENSP00000386088	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17455 AN: 152110 Hom.: 1164 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.115 AC: 17486 AN: 152228 Hom.: 1167 Cov.: 32 AF XY: 0.110 AC XY: 8161 AN XY: 74442

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0476

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0951

Alfa AF: 0.101 Hom.: 221

Bravo AF: 0.116

Asia WGS AF: 0.0570 AC: 195 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs17031005; hg19: chr2-43761299;