rs2405942

Positions:

• chrX-9846095-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001649.4(SHROOM2):​c.166-27557G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.78 (23654 hom., 21139 hem., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: SHROOM2 NM_001649.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM2	NM_001649.4	c.166-27557G>A		intron_variant		ENST00000380913.8	NP_001640.1
SHROOM2	XM_005274500.5	c.166-27557G>A		intron_variant			XP_005274557.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM2	ENST00000380913.8	c.166-27557G>A		intron_variant		1	NM_001649.4	ENSP00000370299.3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 81444 AN: 104771 Hom.: 23645 Cov.: 19 AF XY: 0.768 AC XY: 21101 AN XY: 27459

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.760

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.802

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.777 AC: 81487 AN: 104830 Hom.: 23654 Cov.: 19 AF XY: 0.768 AC XY: 21139 AN XY: 27528

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.804

Alfa AF: 0.788 Hom.: 49177

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.33
DANN	Benign	0.28

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: rs2405942; hg19: chrX-9814135;