Variant X-53234372-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP7BS1_Supporting

The NM_001111125.3(IQSEC2):c.4314A>C(p.Pro1438=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0067 ( 0 hom., 0 hem., cov: 0)

Exomes 𝑓: 0.0034 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IQSEC2
NM_001111125.3 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.280

Variant links:

Genes affected

IQSEC2 (HGNC:29059): (IQ motif and Sec7 domain ArfGEF 2) This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

IQSEC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-0.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0034 (392/115345) while in subpopulation AMR AF= 0.0182 (21/1155). AF 95% confidence interval is 0.0122. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. Median coverage is 6. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC2	NM_001111125.3 linkuse as main transcript	c.4314A>C	p.Pro1438=	synonymous_variant	15/15	ENST00000642864.1	NP_001104595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC2	ENST00000642864.1 linkuse as main transcript	c.4314A>C	p.Pro1438=	synonymous_variant	15/15		NM_001111125.3	ENSP00000495726	P1	Q5JU85-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

8069

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681

FAILED QC

Gnomad AFR

AF:

0.00617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00382

Gnomad ASJ

AF:

0.00840

Gnomad EAS

AF:

0.00599

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00340

AC:

392

AN:

115345

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20029

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.00548

Gnomad4 EAS exome

AF:

0.00376

Gnomad4 SAS exome

AF:

0.00759

Gnomad4 FIN exome

AF:

0.00398

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.00691

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00669

AC:

AN:

8072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682

show subpopulations

Gnomad4 AFR

AF:

0.00617

Gnomad4 AMR

AF:

0.00382

Gnomad4 ASJ

AF:

0.00840

Gnomad4 EAS

AF:

0.00592

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0253

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2015	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 12, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.92

DANN

Benign

0.44

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