2-43410859-A-G

Variant names:

• chr2-43410859-A-G
• rs7591218
• NM_022065.5:c.4059-12720T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.4059-12720T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,032 control chromosomes in the GnomAD database, including 32,975 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 0.65 (32975 hom., cov: 31)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.4059-12720T>C		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.4059-12720T>C		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.4059-12720T>C		intron	N/A	NP_001332854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.4059-12720T>C		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.4059-12720T>C		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*3154-12720T>C		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98995 AN: 151914 Hom.: 32965 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.652 AC: 99054 AN: 152032 Hom.: 32975 Cov.: 31 AF XY: 0.647 AC XY: 48070 AN XY: 74310

African (AFR) AF: 0.675 AC: 27983 AN: 41474

American (AMR) AF: 0.504 AC: 7694 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2542 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1507 AN: 5178

South Asian (SAS) AF: 0.700 AC: 3377 AN: 4822

European-Finnish (FIN) AF: 0.653 AC: 6898 AN: 10564

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46888 AN: 67956

Other (OTH) AF: 0.651 AC: 1373 AN: 2108

Alfa AF: 0.662 Hom.: 12571

Bravo AF: 0.636

Asia WGS AF: 0.518 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.87
PhyloP100		-0.54
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: rs7591218; hg19: chr2-43637998;