chr1-7849677-C-G

Variant names:

• chr1-7849677-C-G
• rs2890565
• NM_006786.4:c.221G>C

Variant summary

Our verdict is Likely benign. The variant received -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. 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. 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
• Publications: 48 publications found

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

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=0.050144047).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006786.4. 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
	UTS2	NM_006786.4	MANE Select	c.221G>C	p.Ser74Thr	missense	Exon 3 of 4	NP_006777.1
	UTS2	NM_021995.2		c.266G>C	p.Ser89Thr	missense	Exon 4 of 5	NP_068835.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTS2	ENST00000361696.10	TSL:1 MANE Select	c.221G>C	p.Ser74Thr	missense	Exon 3 of 4	ENSP00000355163.5
	UTS2	ENST00000054668.5	TSL:1	c.266G>C	p.Ser89Thr	missense	Exon 4 of 5	ENSP00000054668.5
	UTS2	ENST00000377516.6	TSL:5	c.221G>C	p.Ser74Thr	missense	Exon 4 of 7	ENSP00000366738.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.48
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.035
Sift	Benign	0.61	T
Sift4G	Benign	0.61	T
Polyphen		0.0070	B
Vest4		0.089
MutPred		0.13		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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2890565; hg19: chr1-7909737;