2-43446177-C-G

Position:

• chr2-43446177-C-G

Variant summary

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

The NM_022065.5(THADA):​c.3837-15875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,154 control chromosomes in the GnomAD database, including 40,458 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 0.73 (40458 hom., cov: 34)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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]

THADA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5	c.3837-15875G>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.3837-15875G>C		intron_variant		1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110601 AN: 152036 Hom.: 40417 Cov.: 34

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.728 AC: 110697 AN: 152154 Hom.: 40458 Cov.: 34 AF XY: 0.728 AC XY: 54179 AN XY: 74382

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.730

Alfa AF: 0.690 Hom.: 4298

Bravo AF: 0.735

Asia WGS AF: 0.692 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.66

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: rs10200833; hg19: chr2-43673316;