1-7849677-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006786.4(UTS2):​c.221G>A​(p.Ser74Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,607,856 control chromosomes in the GnomAD database, including 4,932 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 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: 𝑓 0.059 (691 hom., cov: 32)
  • Exomes 𝑓: 0.045 (4241 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

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>A	p.Ser74Asn	missense	Exon 3 of 4	NP_006777.1
	UTS2	NM_021995.2		c.266G>A	p.Ser89Asn	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>A	p.Ser74Asn	missense	Exon 3 of 4	ENSP00000355163.5
	UTS2	ENST00000054668.5	TSL:1	c.266G>A	p.Ser89Asn	missense	Exon 4 of 5	ENSP00000054668.5
	UTS2	ENST00000377516.6	TSL:5	c.221G>A	p.Ser74Asn	missense	Exon 4 of 7	ENSP00000366738.2

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9025 AN: 152122 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.00915

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0300

Gnomad OTH AF: 0.0627

GnomAD2 exomes AF: 0.0875 AC: 21533 AN: 246126 AF XY: 0.0766

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0286

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0448 AC: 65145 AN: 1455616 Hom.: 4241 Cov.: 30 AF XY: 0.0438 AC XY: 31713 AN XY: 724264

African (AFR) AF: 0.0477 AC: 1583 AN: 33206

American (AMR) AF: 0.302 AC: 12749 AN: 42220

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 976 AN: 26054

East Asian (EAS) AF: 0.245 AC: 9595 AN: 39224

South Asian (SAS) AF: 0.0502 AC: 4280 AN: 85288

European-Finnish (FIN) AF: 0.0134 AC: 715 AN: 53338

Middle Eastern (MID) AF: 0.0316 AC: 182 AN: 5752

European-Non Finnish (NFE) AF: 0.0286 AC: 31808 AN: 1110378

Other (OTH) AF: 0.0541 AC: 3257 AN: 60156

GnomAD4 genome AF: 0.0594 AC: 9039 AN: 152240 Hom.: 691 Cov.: 32 AF XY: 0.0629 AC XY: 4684 AN XY: 74430

African (AFR) AF: 0.0471 AC: 1956 AN: 41556

American (AMR) AF: 0.191 AC: 2927 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5176

South Asian (SAS) AF: 0.0540 AC: 260 AN: 4818

European-Finnish (FIN) AF: 0.00915 AC: 97 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2040 AN: 68014

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

Alfa AF: 0.0456 Hom.: 1563

Bravo AF: 0.0774

TwinsUK AF: 0.0275 AC: 102

ALSPAC AF: 0.0283 AC: 109

ESP6500AA AF: 0.0513 AC: 226

ESP6500EA AF: 0.0293 AC: 252

ExAC AF: 0.0830 AC: 10076

Asia WGS AF: 0.178 AC: 618 AN: 3478

EpiCase AF: 0.0311

EpiControl AF: 0.0306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.92
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.48
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.062
Sift	Benign	0.072	T
Sift4G	Benign	0.19	T
Polyphen		0.56	P
Vest4		0.050
MPC		0.22
ClinPred		0.0028	T
GERP RS		-0.92
Varity_R		0.055
gMVP		0.024
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 6

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

Other links and lift over

dbSNP: rs2890565; hg19: chr1-7909737; COSMIC: COSV50013136; COSMIC: COSV50013136;