chr10-5720876-A-C

Variant names:

• chr10-5720876-A-C
• rs1002993033
• NM_001321783.2:c.52A>C

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.52A>C​(p.Met18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,840 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. M18V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TASOR2 NM_001321783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• 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=0.049946398).

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.52A>C	p.Met18Leu	missense	Exon 7 of 22	NP_001308712.2	Q5VWN6-1
	TASOR2	NM_001387328.1		c.697A>C	p.Met233Leu	missense	Exon 9 of 24	NP_001374257.1	A0A2R8YH03
	TASOR2	NM_001321784.2		c.52A>C	p.Met18Leu	missense	Exon 7 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.52A>C	p.Met18Leu	missense	Exon 7 of 22	ENSP00000512130.1	Q5VWN6-1
	TASOR2	ENST00000328090.9	TSL:1	c.52A>C	p.Met18Leu	missense	Exon 6 of 21	ENSP00000328426.5	Q5VWN6-1
	TASOR2	ENST00000699051.1		c.835A>C	p.Met279Leu	missense	Exon 10 of 25	ENSP00000514102.1	A0A8V8TMN1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245608 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457840 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724864

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 84634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110888

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.0
DANN	Benign	0.81
DEOGEN2	Benign	0.00089	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.54
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.039
Sift	Benign	0.052	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.40		Loss of methylation at K22 (P = 0.0754)
MVP		0.30
MPC		0.042
ClinPred		0.022	T
GERP RS		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.27
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1002993033; hg19: chr10-5762839;