chr2-43505684-T-C

Position:

• chr2-43505684-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022065.5(THADA):​c.3559A>G​(p.Thr1187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,593,848 control chromosomes in the GnomAD database, including 11,113 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1998 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9115 hom.)
• Consequence: THADA NM_022065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019688606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5	c.3559A>G	p.Thr1187Ala	missense_variant	24/38	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.3559A>G	p.Thr1187Ala	missense_variant	24/38	1	NM_022065.5	ENSP00000386088	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21313 AN: 152144 Hom.: 1986 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00672

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0990 AC: 21766 AN: 219906 Hom.: 1424 AF XY: 0.100 AC XY: 11828 AN XY: 117810

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.00576

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.0510

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0960

GnomAD4 exome AF: 0.106 AC: 153003 AN: 1441586 Hom.: 9115 Cov.: 30 AF XY: 0.107 AC XY: 76205 AN XY: 714672

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.0585

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.00779

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.0530

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.140 AC: 21364 AN: 152262 Hom.: 1998 Cov.: 32 AF XY: 0.134 AC XY: 9984 AN XY: 74450

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.0811

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00674

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.112

Alfa AF: 0.110 Hom.: 2592

Bravo AF: 0.146

TwinsUK AF: 0.107 AC: 398

ALSPAC AF: 0.115 AC: 444

ESP6500AA AF: 0.260 AC: 968

ESP6500EA AF: 0.110 AC: 897

ExAC AF: 0.0971 AC: 11681

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	.;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.00085	P;P;P;P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.094
Sift	Benign	0.089	T;T
Sift4G	Benign	0.080	T;T
Polyphen		0.17	B;B
Vest4		0.15
ClinPred		0.014	T
GERP RS		5.5
Varity_R		0.26
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs7578597; hg19: chr2-43732823; COSMIC: COSV57682006; COSMIC: COSV57682006;