2-43230958-G-T

Variant names:

• chr2-43230958-G-T
• rs114015985
• NM_022065.5:c.5852C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022065.5(THADA):​c.5852C>A​(p.Ala1951Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A1951G) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: THADA NM_022065.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04306221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022065.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	NM_022065.5	MANE Select	c.5852C>A	p.Ala1951Glu	missense	Exon 38 of 38	NP_071348.3
	THADA	NM_001083953.2		c.5852C>A	p.Ala1951Glu	missense	Exon 38 of 38	NP_001077422.1	Q6YHU6-1
	THADA	NM_001345925.2		c.5852C>A	p.Ala1951Glu	missense	Exon 39 of 39	NP_001332854.1	Q6YHU6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THADA	ENST00000405975.7	TSL:1 MANE Select	c.5852C>A	p.Ala1951Glu	missense	Exon 38 of 38	ENSP00000386088.2	Q6YHU6-1
	THADA	ENST00000405006.8	TSL:1	c.5852C>A	p.Ala1951Glu	missense	Exon 38 of 38	ENSP00000385995.4	Q6YHU6-1
	THADA	ENST00000855634.1		c.5852C>A	p.Ala1951Glu	missense	Exon 39 of 39	ENSP00000525693.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.4
DANN	Benign	0.81
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.13
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.13
Sift	Uncertain	0.020	D
Sift4G	Benign	0.15	T
Polyphen		0.11	B
Vest4		0.22
MutPred		0.10		Gain of solvent accessibility (P = 0.0456)
MVP		0.014
ClinPred		0.053	T
GERP RS		-0.68
Varity_R		0.054
gMVP		0.20
Mutation Taster		=99/1	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: rs114015985; hg19: chr2-43458097;