chr2-43559136-G-A

Variant names:

• chr2-43559136-G-A
• rs17413525
• NM_022065.5:c.2463+1098C>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.2463+1098C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,256 control chromosomes in the GnomAD database, including 486 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 0.068 (486 hom., cov: 32)
• Consequence: THADA NM_022065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0911 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.2463+1098C>T		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.2463+1098C>T		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.2463+1098C>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.2463+1098C>T		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.2463+1098C>T		intron	N/A	ENSP00000385995.4
	THADA	ENST00000404790.5	TSL:1	c.2463+1098C>T		intron	N/A	ENSP00000384266.1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10353 AN: 152138 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0301

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0680 AC: 10356 AN: 152256 Hom.: 486 Cov.: 32 AF XY: 0.0694 AC XY: 5165 AN XY: 74426

African (AFR) AF: 0.0162 AC: 672 AN: 41580

American (AMR) AF: 0.0699 AC: 1069 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6325 AN: 68008

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0457 Hom.: 43

Bravo AF: 0.0629

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.36
PhyloP100		-0.069
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: rs17413525; hg19: chr2-43786275;