7-2559184-G-A

Position:

• chr7-2559184-G-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_152558.5(IQCE):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQCE NM_152558.5 start_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.79

Genes affected

IQCE (HGNC:29171): (IQ motif containing E) Involved in limb morphogenesis. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-2559184-G-A is Pathogenic according to our data. Variant chr7-2559184-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1030264.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCE	NM_152558.5	c.3G>A	p.Met1?	start_lost	1/22	ENST00000402050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCE	ENST00000402050.7	c.3G>A	p.Met1?	start_lost	1/22	1	NM_152558.5	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1064276 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 502610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polydactyly, postaxial, type a7 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 03, 2020

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T;.;T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.2	N;N;N;.;N;.
REVEL	Benign	0.19
Sift	Uncertain	0.024	D;D;D;.;D;.
Sift4G	Uncertain	0.052	T;D;D;D;D;D
Polyphen		0.075	B;.;B;.;.;.
Vest4		0.84
MutPred		0.83		Gain of catalytic residue at M1 (P = 0.01);Gain of catalytic residue at M1 (P = 0.01);Gain of catalytic residue at M1 (P = 0.01);Gain of catalytic residue at M1 (P = 0.01);Gain of catalytic residue at M1 (P = 0.01);Gain of catalytic residue at M1 (P = 0.01);
MVP		0.38
ClinPred		0.63	D
GERP RS		3.1
Varity_R		0.45
gMVP		0.062

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: rs1298717770; hg19: chr7-2598818;