rs765254477

Variant names:

• chr2-43231228-C-A
• rs765254477
• NM_022065.5:c.5582G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-43231228-C-A
• chr2-43231228-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022065.5(THADA):​c.5582G>T​(p.Arg1861Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1861H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THADA NM_022065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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]

ENSG00000234936 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044436425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.5582G>T	p.Arg1861Leu	missense_variant	Exon 38 of 38	ENST00000405975.7	NP_071348.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7	c.5582G>T	p.Arg1861Leu	missense_variant	Exon 38 of 38	1	NM_022065.5	ENSP00000386088.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.052
DANN	Benign	0.95
DEOGEN2	Benign	0.00083	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.021
Sift	Benign	0.40	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.30		Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);
MVP		0.014
ClinPred		0.040	T
GERP RS		-6.5
Varity_R		0.023
gMVP		0.13

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: rs765254477; hg19: chr2-43458367;