2-43279806-A-G

Position:

• chr2-43279806-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022065.5(THADA):​c.5255T>C​(p.Val1752Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.27

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THADA	NM_022065.5	c.5255T>C	p.Val1752Ala	missense_variant	36/38	ENST00000405975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THADA	ENST00000405975.7	c.5255T>C	p.Val1752Ala	missense_variant	36/38	1	NM_022065.5	P1
THADA	ENST00000405006.8	c.5255T>C	p.Val1752Ala	missense_variant	36/38	1		P1
THADA	ENST00000407351.5	c.2975T>C	p.Val992Ala	missense_variant	21/23	2
THADA	ENST00000398653.5	c.*4171T>C		3_prime_UTR_variant, NMD_transcript_variant	34/36	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.5255T>C (p.V1752A) alteration is located in exon 36 (coding exon 35) of the THADA gene. This alteration results from a T to C substitution at nucleotide position 5255, causing the valine (V) at amino acid position 1752 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T;T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.82	P;P
Vest4		0.63
MutPred		0.57		Loss of catalytic residue at V1752 (P = 0.0095);Loss of catalytic residue at V1752 (P = 0.0095);
MVP		0.19
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.099
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-43506945;