10-5739665-T-G

Variant names:

• chr10-5739665-T-G
• rs2254067
• NM_001321783.2:c.1495T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387328.1(TASOR2):​c.2140T>G​(p.Cys714Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,613,460 control chromosomes in the GnomAD database, including 563,167 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. C714S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.85 (54806 hom., cov: 30)
  • Exomes 𝑓: 0.83 (508361 hom.)
• Consequence: TASOR2 NM_001387328.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 33 publications found

Genes affected

TASOR2 (HGNC:23484): (transcription activation suppressor family member 2) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000226647 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1235861E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387328.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR2	NM_001321783.2	MANE Select	c.1495T>G	p.Cys499Gly	missense	Exon 14 of 22	NP_001308712.2
	TASOR2	NM_001387328.1		c.2140T>G	p.Cys714Gly	missense	Exon 16 of 24	NP_001374257.1
	TASOR2	NM_001321784.2		c.1495T>G	p.Cys499Gly	missense	Exon 14 of 22	NP_001308713.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR2	ENST00000695737.1	MANE Select	c.1495T>G	p.Cys499Gly	missense	Exon 14 of 22	ENSP00000512130.1
	TASOR2	ENST00000328090.9	TSL:1	c.1495T>G	p.Cys499Gly	missense	Exon 13 of 21	ENSP00000328426.5
	TASOR2	ENST00000699051.1		c.2278T>G	p.Cys760Gly	missense	Exon 17 of 25	ENSP00000514102.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128918 AN: 151956 Hom.: 54765 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.842

GnomAD2 exomes AF: 0.838 AC: 209041 AN: 249342 AF XY: 0.833

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.903

Gnomad ASJ exome AF: 0.766

Gnomad EAS exome AF: 0.809

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.833

Gnomad OTH exome AF: 0.836

GnomAD4 exome AF: 0.833 AC: 1217964 AN: 1461386 Hom.: 508361 Cov.: 47 AF XY: 0.831 AC XY: 603869 AN XY: 726938

African (AFR) AF: 0.879 AC: 29417 AN: 33468

American (AMR) AF: 0.902 AC: 40317 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 20346 AN: 26134

East Asian (EAS) AF: 0.790 AC: 31354 AN: 39690

South Asian (SAS) AF: 0.780 AC: 67246 AN: 86240

European-Finnish (FIN) AF: 0.867 AC: 46321 AN: 53412

Middle Eastern (MID) AF: 0.816 AC: 4708 AN: 5768

European-Non Finnish (NFE) AF: 0.835 AC: 928323 AN: 1111570

Other (OTH) AF: 0.827 AC: 49932 AN: 60382

GnomAD4 genome AF: 0.848 AC: 129012 AN: 152074 Hom.: 54806 Cov.: 30 AF XY: 0.850 AC XY: 63154 AN XY: 74330

African (AFR) AF: 0.876 AC: 36332 AN: 41484

American (AMR) AF: 0.863 AC: 13184 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2685 AN: 3468

East Asian (EAS) AF: 0.811 AC: 4192 AN: 5166

South Asian (SAS) AF: 0.775 AC: 3730 AN: 4814

European-Finnish (FIN) AF: 0.882 AC: 9334 AN: 10584

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.836 AC: 56827 AN: 67972

Other (OTH) AF: 0.836 AC: 1761 AN: 2106

Alfa AF: 0.835 Hom.: 213223

Bravo AF: 0.852

TwinsUK AF: 0.835 AC: 3097

ALSPAC AF: 0.834 AC: 3216

ESP6500AA AF: 0.871 AC: 3240

ESP6500EA AF: 0.832 AC: 6829

ExAC AF: 0.837 AC: 101038

Asia WGS AF: 0.783 AC: 2721 AN: 3478

EpiCase AF: 0.830

EpiControl AF: 0.828

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	3.7
DANN	Benign	0.50
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00073	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.38
PrimateAI	Benign	0.28	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.018
MPC		0.050
ClinPred		0.00053	T
GERP RS		2.4
Varity_R		0.026
gMVP		0.092
Mutation Taster		=100/0	polymorphism (auto)

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: rs2254067; hg19: chr10-5781628; COSMIC: COSV107397945;