2-43534160-A-G

Variant names:

• chr2-43534160-A-G
• rs17031005
• NM_022065.5:c.3265-6172T>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.3265-6172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,228 control chromosomes in the GnomAD database, including 1,167 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 0.11 (1167 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 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.3265-6172T>C		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.3265-6172T>C		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.3265-6172T>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.3265-6172T>C		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.3265-6172T>C		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2360-6172T>C		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17455 AN: 152110 Hom.: 1164 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.115 AC: 17486 AN: 152228 Hom.: 1167 Cov.: 32 AF XY: 0.110 AC XY: 8161 AN XY: 74442

African (AFR) AF: 0.176 AC: 7324 AN: 41526

American (AMR) AF: 0.0710 AC: 1086 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3470

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5188

South Asian (SAS) AF: 0.137 AC: 661 AN: 4822

European-Finnish (FIN) AF: 0.0476 AC: 504 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7153 AN: 68016

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.104 Hom.: 269

Bravo AF: 0.116

Asia WGS AF: 0.0570 AC: 195 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.84
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: rs17031005; hg19: chr2-43761299;