rs782547252

chrX-53250710-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001111125.3(IQSEC2):c.1866G>A(p.Glu622=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,097,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000029 (0 hom. 12 hem.)
• Consequence: IQSEC2 NM_001111125.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.300

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-53250710-C-T is Benign according to our data. Variant chrX-53250710-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 538617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQSEC2	NM_001111125.3	c.1866G>A	p.Glu622=	synonymous_variant	5/15	ENST00000642864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQSEC2	ENST00000642864.1	c.1866G>A	p.Glu622=	synonymous_variant	5/15		NM_001111125.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000333 AC: 6 AN: 180147 Hom.: 0 AF XY: 0.0000152 AC XY: 1 AN XY: 65617

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000250

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.0000292 AC: 32 AN: 1097753 Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 12 AN XY: 363203

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000132

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000309

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000416

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, X-linked 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 12, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	11
Dann	Benign	0.56

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: rs782547252; hg19: chrX-53279892;