chr2-43360365-C-T

Variant names:

• chr2-43360365-C-T
• rs6732426
• NM_022065.5:c.4228-16128G>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.4228-16128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,032 control chromosomes in the GnomAD database, including 22,612 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 0.53 (22612 hom., cov: 33)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 25 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.4228-16128G>A		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.4228-16128G>A		intron	N/A	NP_001077422.1	Q6YHU6-1
	THADA	NM_001345925.2		c.4228-16128G>A		intron	N/A	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.4228-16128G>A		intron	N/A	ENSP00000386088.2	Q6YHU6-1
	THADA	ENST00000405006.8	TSL:1	c.4228-16128G>A		intron	N/A	ENSP00000385995.4	Q6YHU6-1
	THADA	ENST00000408045.7	TSL:1	n.*3323-16128G>A		intron	N/A	ENSP00000384172.2	B6ZDE5

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80460 AN: 151914 Hom.: 22572 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.530 AC: 80552 AN: 152032 Hom.: 22612 Cov.: 33 AF XY: 0.523 AC XY: 38865 AN XY: 74320

African (AFR) AF: 0.668 AC: 27685 AN: 41472

American (AMR) AF: 0.374 AC: 5710 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3464

East Asian (EAS) AF: 0.0378 AC: 196 AN: 5180

South Asian (SAS) AF: 0.464 AC: 2233 AN: 4814

European-Finnish (FIN) AF: 0.535 AC: 5649 AN: 10558

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35541 AN: 67952

Other (OTH) AF: 0.497 AC: 1051 AN: 2116

Alfa AF: 0.512 Hom.: 49994

Bravo AF: 0.519

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		-0.16
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: rs6732426; hg19: chr2-43587504;