chr1-7849677-C-G

Position:

• chr1-7849677-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006786.4(UTS2):​c.221G>C​(p.Ser74Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. S74G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTS2 NM_006786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

Genes affected

UTS2 (HGNC:12636): (urotensin 2) This gene encodes a mature peptide that is an active cyclic heptapeptide absolutely conserved from lamprey to human. The active peptide acts as a vasoconstrictor and is expressed only in brain tissue. Despite the gene family name similarity, this gene is not homologous to urocortin, a member of the sauvagine/corticotropin-releasing factor/urotensin I family. Most of the proprotein is cleaved to make the mature peptide. Transcript variants encoding different preproprotein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050144047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTS2	NM_006786.4	c.221G>C	p.Ser74Thr	missense_variant	3/4	ENST00000361696.10
UTS2	NM_021995.2	c.266G>C	p.Ser89Thr	missense_variant	4/5
UTS2	XM_011540537.3	c.266G>C	p.Ser89Thr	missense_variant	5/6
UTS2	XM_011540538.2	c.221G>C	p.Ser74Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTS2	ENST00000361696.10	c.221G>C	p.Ser74Thr	missense_variant	3/4	1	NM_006786.4	P2
UTS2	ENST00000054668.5	c.266G>C	p.Ser89Thr	missense_variant	4/5	1		A2
UTS2	ENST00000377516.6	c.221G>C	p.Ser74Thr	missense_variant	4/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.81
DANN	Benign	0.61
DEOGEN2	Benign	0.048	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.35	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.61	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.089
MutPred		0.13		Loss of disorder (P = 0.0707);Loss of disorder (P = 0.0707);.;
MVP		0.12
MPC		0.19
ClinPred		0.058	T
GERP RS		-0.92
Varity_R		0.038
gMVP		0.037

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2890565; hg19: chr1-7909737;