2-43446177-C-G

Variant names:

• chr2-43446177-C-G
• rs10200833
• NM_022065.5:c.3837-15875G>C

Variant summary

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

The ENST00000405975.7(THADA):​c.3837-15875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,154 control chromosomes in the GnomAD database, including 40,458 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 0.73 (40458 hom., cov: 34)
• Consequence: THADA ENST00000405975.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405975.7. 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.3837-15875G>C		intron	N/A	NP_071348.3
	THADA	NM_001083953.2		c.3837-15875G>C		intron	N/A	NP_001077422.1
	THADA	NM_001345925.2		c.3837-15875G>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.3837-15875G>C		intron	N/A	ENSP00000386088.2
	THADA	ENST00000405006.8	TSL:1	c.3837-15875G>C		intron	N/A	ENSP00000385995.4
	THADA	ENST00000408045.7	TSL:1	n.*2932-15875G>C		intron	N/A	ENSP00000384172.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110601 AN: 152036 Hom.: 40417 Cov.: 34

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.728 AC: 110697 AN: 152154 Hom.: 40458 Cov.: 34 AF XY: 0.728 AC XY: 54179 AN XY: 74382

African (AFR) AF: 0.759 AC: 31523 AN: 41508

American (AMR) AF: 0.774 AC: 11843 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2434 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3872 AN: 5182

South Asian (SAS) AF: 0.702 AC: 3385 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7497 AN: 10574

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47667 AN: 67986

Other (OTH) AF: 0.730 AC: 1542 AN: 2112

Alfa AF: 0.690 Hom.: 4298

Bravo AF: 0.735

Asia WGS AF: 0.692 AC: 2408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.22
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: rs10200833; hg19: chr2-43673316;