17-64641301-A-G

Position:

• chr17-64641301-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022739.4(SMURF2):​c.52+20528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,228 control chromosomes in the GnomAD database, including 317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (317 hom., cov: 32)
• Consequence: SMURF2 NM_022739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMURF2	NM_022739.4	c.52+20528T>C		intron_variant		ENST00000262435.14	NP_073576.1
SMURF2	XM_005257585.4	c.52+20528T>C		intron_variant			XP_005257642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMURF2	ENST00000262435.14	c.52+20528T>C		intron_variant		1	NM_022739.4	ENSP00000262435	P1

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7648 AN: 152110 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0502 AC: 7646 AN: 152228 Hom.: 317 Cov.: 32 AF XY: 0.0534 AC XY: 3977 AN XY: 74440

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0475

Gnomad4 NFE AF: 0.0406

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0503 Hom.: 33

Bravo AF: 0.0523

Asia WGS AF: 0.0330 AC: 114 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs16947956; hg19: chr17-62637419;