Variant chr17-64571869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_022739.4(SMURF2):c.945C>T(p.Phe315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,613,718 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 193 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 207 hom. )

Consequence

SMURF2
NM_022739.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

SMURF2 (HGNC:16809): (SMAD specific E3 ubiquitin protein ligase 2) Enables SMAD binding activity; identical protein binding activity; and ubiquitin-protein transferase activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of trophoblast cell migration; and ubiquitin-dependent SMAD protein catabolic process. Located in nuclear speck. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

SMURF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-64571869-G-A is Benign according to our data. Variant chr17-64571869-G-A is described in ClinVar as [Benign]. Clinvar id is 777211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMURF2	NM_022739.4 linkuse as main transcript	c.945C>T	p.Phe315=	synonymous_variant	10/19	ENST00000262435.14	NP_073576.1
SMURF2	XM_047436546.1 linkuse as main transcript	c.951C>T	p.Phe317=	synonymous_variant	10/19		XP_047292502.1
SMURF2	XM_005257585.4 linkuse as main transcript	c.906C>T	p.Phe302=	synonymous_variant	9/18		XP_005257642.1
SMURF2	XR_007065425.1 linkuse as main transcript	n.4115C>T		non_coding_transcript_exon_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMURF2	ENST00000262435.14 linkuse as main transcript	c.945C>T	p.Phe315=	synonymous_variant	10/19	1	NM_022739.4	ENSP00000262435	P1

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4189

AN:

152122

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0955

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.00746

AC:

1871

AN:

250928

Hom.:

AF XY:

0.00523

AC XY:

710

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00296

AC:

4333

AN:

1461478

Hom.:

207

Cov.:

AF XY:

0.00257

AC XY:

1867

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.00605

GnomAD4 genome

AF:

0.0276

AC:

4204

AN:

152240

Hom.:

193

Cov.:

AF XY:

0.0266

AC XY:

1978

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0955

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 20, 2018	- -

SMURF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over