10-5730622-G-T

Variant names:

• chr10-5730622-G-T
• rs746590270
• NM_001321783.2:c.623G>T

Variant summary

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

The NM_001321783.2(TASOR2):​c.623G>T​(p.Arg208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 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. R208H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TASOR2 NM_001321783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 0 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: 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=0.05124834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321783.2. 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
	TASOR2	NM_001321783.2	MANE Select	c.623G>T	p.Arg208Leu	missense	Exon 12 of 22	NP_001308712.2	Q5VWN6-1
	TASOR2	NM_001387328.1		c.1268G>T	p.Arg423Leu	missense	Exon 14 of 24	NP_001374257.1	A0A2R8YH03
	TASOR2	NM_001321784.2		c.623G>T	p.Arg208Leu	missense	Exon 12 of 22	NP_001308713.2	Q5VWN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR2	ENST00000695737.1	MANE Select	c.623G>T	p.Arg208Leu	missense	Exon 12 of 22	ENSP00000512130.1	Q5VWN6-1
	TASOR2	ENST00000328090.9	TSL:1	c.623G>T	p.Arg208Leu	missense	Exon 11 of 21	ENSP00000328426.5	Q5VWN6-1
	TASOR2	ENST00000699051.1		c.1406G>T	p.Arg469Leu	missense	Exon 15 of 25	ENSP00000514102.1	A0A8V8TMN1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.84
DANN	Benign	0.84
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.13
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.027	D
Polyphen		0.39	B
Vest4		0.44
MutPred		0.38		Gain of helix (P = 0.0022)
MVP		0.13
MPC		0.053
ClinPred		0.10	T
GERP RS		-8.1
PromoterAI		-0.065	Neutral
Varity_R		0.062
gMVP		0.19
Mutation Taster		=86/14	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: rs746590270; hg19: chr10-5772585;