Variant 2-43230958-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_022065.5(THADA):c.5852C>G(p.Ala1951Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,604,270 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

THADA
NM_022065.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.125

Variant links:

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]

THADA links:

THADA (HGNC:):

THADA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031399727).

BP6

Variant 2-43230958-G-C is Benign according to our data. Variant chr2-43230958-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3043703.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THADA	NM_022065.5 linkuse as main transcript	c.5852C>G	p.Ala1951Gly	missense_variant	38/38	ENST00000405975.7	NP_071348.3	Q6YHU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THADA	ENST00000405975.7 linkuse as main transcript	c.5852C>G	p.Ala1951Gly	missense_variant	38/38	1	NM_022065.5	ENSP00000386088.2		Q6YHU6-1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00582

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000388

AC:

AN:

247348

Hom.:

AF XY:

0.000253

AC XY:

AN XY:

134208

show subpopulations

Gnomad AFR exome

AF:

0.00518

Gnomad AMR exome

AF:

0.000324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000182

AC:

265

AN:

1452072

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

121

AN XY:

720392

show subpopulations

Gnomad4 AFR exome

AF:

0.00650

Gnomad4 AMR exome

AF:

0.000271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000996

Gnomad4 OTH exome

AF:

0.000367

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

152198

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00588

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000672

Hom.:

Bravo

AF:

0.00172

ESP6500AA

AF:

0.00451

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000455

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

THADA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.2

DANN

Benign

0.86

DEOGEN2

Benign

0.0011

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.11

Sift

Benign

0.058

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.093

B;B

Vest4

0.10

MVP

0.014

ClinPred

0.0048

GERP RS

-0.68

Varity_R

0.023

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over