2-43326810-T-C

Position:

• chr2-43326810-T-C

Variant summary

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

The NM_022065.5(THADA):​c.4344-6270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,146 control chromosomes in the GnomAD database, including 48,417 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 0.79 (48417 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5	c.4344-6270A>G		intron_variant		ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.4344-6270A>G		intron_variant		1	NM_022065.5	ENSP00000386088	P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119821 AN: 152028 Hom.: 48372 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.788 AC: 119921 AN: 152146 Hom.: 48417 Cov.: 31 AF XY: 0.784 AC XY: 58334 AN XY: 74390

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.763

Alfa AF: 0.774 Hom.: 75129

Bravo AF: 0.774

Asia WGS AF: 0.567 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.79

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: rs1465618; hg19: chr2-43553949;