Variant X-9894391-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001649.4(SHROOM2):c.483G>A(p.Glu161Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,208,313 control chromosomes in the GnomAD database, including 54 homozygotes. There are 737 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., 352 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 25 hom. 385 hem. )

Consequence

SHROOM2
NM_001649.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.968

Variant links:

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]

SHROOM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-9894391-G-A is Benign according to our data. Variant chrX-9894391-G-A is described in ClinVar as [Benign]. Clinvar id is 3042208.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-9894391-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.968 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1341/111376) while in subpopulation AFR AF= 0.0414 (1267/30608). AF 95% confidence interval is 0.0395. There are 29 homozygotes in gnomad4. There are 352 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM2	NM_001649.4 link	c.483G>A	p.Glu161Glu	synonymous_variant	4/10	ENST00000380913.8	NP_001640.1	Q13796
SHROOM2	XM_005274500.5 link	c.483G>A	p.Glu161Glu	synonymous_variant	4/10		XP_005274557.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM2	ENST00000380913.8 link	c.483G>A	p.Glu161Glu	synonymous_variant	4/10	1	NM_001649.4	ENSP00000370299.3		Q13796

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1337

AN:

111325

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

352

AN XY:

33543

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00457

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000245

Gnomad OTH

AF:

0.00880

GnomAD3 exomes

AF:

0.00334

AC:

604

AN:

180748

Hom.:

AF XY:

0.00228

AC XY:

150

AN XY:

65656

show subpopulations

Gnomad AFR exome

AF:

0.0404

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000997

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00130

AC:

1424

AN:

1096937

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

385

AN XY:

362429

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000535

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.0120

AC:

1341

AN:

111376

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

352

AN XY:

33604

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.00456

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000245

Gnomad4 OTH

AF:

0.00869

Alfa

AF:

0.00479

Hom.:

Bravo

AF:

0.0138

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SHROOM2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 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

-0.54

CADD

Benign

1.7

DANN

Benign

0.35

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