2-43494815-G-A

Variant names:

• chr2-43494815-G-A
• rs13431070
• NM_022065.5:c.3744+4018C>T

Variant summary

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

The NM_022065.5(THADA):​c.3744+4018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,100 control chromosomes in the GnomAD database, including 3,362 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 0.17 (3362 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 15 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.3744+4018C>T		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.3744+4018C>T		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.3744+4018C>T		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.3744+4018C>T		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.3744+4018C>T		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2839+4018C>T		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26143 AN: 151982 Hom.: 3337 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.172 AC: 26211 AN: 152100 Hom.: 3362 Cov.: 32 AF XY: 0.165 AC XY: 12268 AN XY: 74370

African (AFR) AF: 0.358 AC: 14833 AN: 41444

American (AMR) AF: 0.100 AC: 1536 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5184

South Asian (SAS) AF: 0.137 AC: 663 AN: 4826

European-Finnish (FIN) AF: 0.0545 AC: 577 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7667 AN: 67984

Other (OTH) AF: 0.141 AC: 298 AN: 2116

Alfa AF: 0.0839 Hom.: 190

Bravo AF: 0.181

Asia WGS AF: 0.0750 AC: 263 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		1.7
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: rs13431070; hg19: chr2-43721954;