2-43506370-G-T

Variant names:

• chr2-43506370-G-T
• rs17030946
• NM_022065.5:c.3508-635C>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.3508-635C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,170 control chromosomes in the GnomAD database, including 581 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 0.083 (581 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 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.3508-635C>A		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.3508-635C>A		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.3508-635C>A		intron	N/A	NP_001332854.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.3508-635C>A		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.3508-635C>A		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2603-635C>A		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.0831 AC: 12641 AN: 152052 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0831 AC: 12642 AN: 152170 Hom.: 581 Cov.: 32 AF XY: 0.0797 AC XY: 5927 AN XY: 74400

African (AFR) AF: 0.0665 AC: 2759 AN: 41510

American (AMR) AF: 0.0604 AC: 923 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.00674 AC: 35 AN: 5190

South Asian (SAS) AF: 0.131 AC: 632 AN: 4816

European-Finnish (FIN) AF: 0.0477 AC: 505 AN: 10590

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.105 AC: 7122 AN: 67986

Other (OTH) AF: 0.0726 AC: 153 AN: 2108

Alfa AF: 0.0446 Hom.: 48

Bravo AF: 0.0798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		0.29
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: rs17030946; hg19: chr2-43733509;