10-5762568-G-C

Variant names:

• chr10-5762568-G-C
• rs2797501
• NM_001321783.2:c.7211G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321783.2(TASOR2):​c.7211G>C​(p.Ser2404Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000081 in 1,234,768 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.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: TASOR2 NM_001321783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 40 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13566673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TASOR2	NM_001321783.2	c.7211G>C	p.Ser2404Thr	missense_variant	Exon 21 of 22	ENST00000695737.1	NP_001308712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TASOR2	ENST00000695737.1	c.7211G>C	p.Ser2404Thr	missense_variant	Exon 21 of 22		NM_001321783.2	ENSP00000512130.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 8.10e-7 AC: 1 AN: 1234768 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 619706

⚠️ 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: 25164

American (AMR) AF: 0.00 AC: 0 AN: 26938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22944

East Asian (EAS) AF: 0.00 AC: 0 AN: 33398

South Asian (SAS) AF: 0.00 AC: 0 AN: 68572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5072

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 949846

Other (OTH) AF: 0.00 AC: 0 AN: 51646

⚠️ 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.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0034	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		0.21
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.042
Sift	Uncertain	0.018	D;.
Sift4G	Benign	0.063	T;.
Polyphen		0.92	P;.
Vest4		0.25
MutPred		0.29		Loss of glycosylation at S2404 (P = 0.0174);.;
MVP		0.082
MPC		0.11
ClinPred		0.70	D
GERP RS		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.31
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2797501; hg19: chr10-5804531;