rs1055252

Positions:

• chr13-26044784-G-A
• chr13-26044784-G-T

Variant summary

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

The NM_001007538.2(SHISA2):​c.*1729C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,130 control chromosomes in the GnomAD database, including 3,307 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 0.19 (3307 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SHISA2 NM_001007538.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

SHISA2 (HGNC:20366): (shisa family member 2) Predicted to be involved in negative regulation of Wnt signaling pathway and negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA2	NM_001007538.2	c.*1729C>T		3_prime_UTR_variant	2/2	ENST00000319420.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA2	ENST00000319420.4	c.*1729C>T		3_prime_UTR_variant	2/2	1	NM_001007538.2	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29327 AN: 152012 Hom.: 3310 Cov.: 33

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.207

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.193 AC: 29330 AN: 152130 Hom.: 3307 Cov.: 33 AF XY: 0.198 AC XY: 14753 AN XY: 74378

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.207

Alfa AF: 0.233 Hom.: 5738

Bravo AF: 0.184

Asia WGS AF: 0.178 AC: 618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.50

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: rs1055252; hg19: chr13-26618922;