X-53227029-C-T

Position:

• chrX-53227029-C-T

Variant summary

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

The ENST00000639796.1(IQSEC2):​c.*817G>A variant causes a 3 prime UTR 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 0.81 (27401 hom., 26083 hem., cov: 22)
  • Exomes 𝑓: 0.75 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: IQSEC2 ENST00000639796.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC2	XM_006724582.5	c.*795G>A		3_prime_UTR_variant	16/16		XP_006724645.1
IQSEC2	XM_047441928.1	c.*817G>A		3_prime_UTR_variant	15/15		XP_047297884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC2	ENST00000638869.1	c.*795G>A		3_prime_UTR_variant	9/9	5		ENSP00000491736.1
IQSEC2	ENST00000639796.1	c.*817G>A		3_prime_UTR_variant	3/3	3		ENSP00000492252.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 88641 AN: 109552 Hom.: 27414 Cov.: 22 AF XY: 0.818 AC XY: 26061 AN XY: 31846

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.957

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 0 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.809 AC: 88641 AN: 109607 Hom.: 27401 Cov.: 22 AF XY: 0.817 AC XY: 26083 AN XY: 31911

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.827

Alfa AF: 0.868 Hom.: 9009

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs942926; hg19: chrX-53256211;