2-43231280-C-T

Variant names:

• chr2-43231280-C-T
• rs2103996032
• NM_022065.5:c.5530G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022065.5(THADA):​c.5530G>A​(p.Val1844Met) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THADA NM_022065.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 0 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]

LINC01126 (HGNC:49275): (long intergenic non-protein coding RNA 1126)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18858647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THADA	NM_022065.5	c.5530G>A	p.Val1844Met	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.5530G>A	p.Val1844Met	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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 05, 2021

New York Genome Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0092	T;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
PhyloP100		2.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.76	N;N
REVEL	Benign	0.085
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.93	P;P
Vest4		0.23
MutPred		0.42		Loss of methylation at K1845 (P = 0.0194);Loss of methylation at K1845 (P = 0.0194);
MVP		0.072
ClinPred		0.48	T
GERP RS		2.1
Varity_R		0.054
gMVP		0.36
Mutation Taster		=95/5	polymorphism

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: rs2103996032; hg19: chr2-43458419;