chr17-64604817-A-T

Variant names:

• chr17-64604817-A-T
• rs111854052
• NM_022739.4:c.91+1785T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022739.4(SMURF2):​c.91+1785T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 151,978 control chromosomes in the GnomAD database, including 11 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 0.012 (11 hom., cov: 31)
• Consequence: SMURF2 NM_022739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

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=-1.0).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1816/151978) while in subpopulation NFE AF= 0.0184 (1247/67950). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4. There are 873 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1816 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMURF2	NM_022739.4	c.91+1785T>A		intron_variant	Intron 2 of 18	ENST00000262435.14	NP_073576.1
SMURF2	XM_047436546.1	c.97+1785T>A		intron_variant	Intron 2 of 18		XP_047292502.1
SMURF2	XM_005257585.4	c.53-6327T>A		intron_variant	Intron 1 of 17		XP_005257642.1
SMURF2	XR_007065425.1	n.3261+1785T>A		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMURF2	ENST00000262435.14	c.91+1785T>A		intron_variant	Intron 2 of 18	1	NM_022739.4	ENSP00000262435.9

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1816 AN: 151860 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.00310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.00870

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0111

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

GnomAD4 genome AF: 0.0119 AC: 1816 AN: 151978 Hom.: 11 Cov.: 31 AF XY: 0.0117 AC XY: 873 AN XY: 74306

Gnomad4 AFR AF: 0.00309

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00312

Gnomad4 FIN AF: 0.00870

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0133 Hom.: 3

Bravo AF: 0.0123

Asia WGS AF: 0.00231 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.2
DANN	Benign	0.60

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: rs111854052; hg19: chr17-62600935;