1-7850818-T-C

Position:

• chr1-7850818-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006786.4(UTS2):​c.208A>G​(p.Lys70Glu) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTS2 NM_006786.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045220405).
• BP6: Variant 1-7850818-T-C is Benign according to our data. Variant chr1-7850818-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2280993.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTS2	NM_006786.4	c.208A>G	p.Lys70Glu	missense_variant	2/4	ENST00000361696.10	NP_006777.1
UTS2	NM_021995.2	c.253A>G	p.Lys85Glu	missense_variant	3/5		NP_068835.1
UTS2	XM_011540537.3	c.253A>G	p.Lys85Glu	missense_variant	4/6		XP_011538839.1
UTS2	XM_011540538.2	c.208A>G	p.Lys70Glu	missense_variant	3/5		XP_011538840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTS2	ENST00000361696.10	c.208A>G	p.Lys70Glu	missense_variant	2/4	1	NM_006786.4	ENSP00000355163	P2
UTS2	ENST00000054668.5	c.253A>G	p.Lys85Glu	missense_variant	3/5	1		ENSP00000054668	A2
UTS2	ENST00000377516.6	c.208A>G	p.Lys70Glu	missense_variant	3/7	5		ENSP00000366738

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.58
DANN	Benign	0.43
DEOGEN2	Benign	0.069	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.095
MutPred		0.19		Loss of ubiquitination at K70 (P = 0.0081);Loss of ubiquitination at K70 (P = 0.0081);.;
MVP		0.11
MPC		0.28
ClinPred		0.049	T
GERP RS		-3.1
Varity_R		0.058
gMVP		0.076

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-7910878;