chr2-43505889-G-T

Variant names:

• chr2-43505889-G-T
• rs7564886
• NM_022065.5:c.3508-154C>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.3508-154C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,164 control chromosomes in the GnomAD database, including 1,572 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 (1572 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.3508-154C>A		intron_variant	Intron 23 of 37	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3508-154C>A		intron_variant	Intron 23 of 37	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19590 AN: 152046 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.129 AC: 19616 AN: 152164 Hom.: 1572 Cov.: 32 AF XY: 0.123 AC XY: 9183 AN XY: 74432

African (AFR) AF: 0.226 AC: 9362 AN: 41482

American (AMR) AF: 0.0766 AC: 1171 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 442 AN: 3466

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5186

South Asian (SAS) AF: 0.132 AC: 635 AN: 4824

European-Finnish (FIN) AF: 0.0480 AC: 509 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7163 AN: 67992

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.115 Hom.: 509

Bravo AF: 0.132

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.56
PhyloP100		0.26
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: rs7564886; hg19: chr2-43733028;