4-102874540-C-G

Position:

• chr4-102874540-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001008388.5(CISD2):​c.103+5353C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 152,064 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CISD2 NM_001008388.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

Genes affected

CISD2 (HGNC:24212): (CDGSH iron sulfur domain 2) The protein encoded by this gene is a zinc finger protein that localizes to the endoplasmic reticulum. The encoded protein binds an iron/sulfur cluster and may be involved in calcium homeostasis. Defects in this gene are a cause of Wolfram syndrome 2. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-102874540-C-G is Benign according to our data. Variant chr4-102874540-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CISD2	NM_001008388.5	c.103+5353C>G		intron_variant		ENST00000273986.10	NP_001008389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CISD2	ENST00000273986.10	c.103+5353C>G		intron_variant		1	NM_001008388.5	ENSP00000273986.4

Frequencies

GnomAD3 genomes AF: 0.00557 AC: 847 AN: 151946 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000895

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00839

Gnomad OTH AF: 0.00430

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00557 AC: 847 AN: 152064 Hom.: 5 Cov.: 32 AF XY: 0.00548 AC XY: 407 AN XY: 74332

Gnomad4 AFR AF: 0.000892

Gnomad4 AMR AF: 0.00720

Gnomad4 ASJ AF: 0.00837

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00312

Gnomad4 FIN AF: 0.00208

Gnomad4 NFE AF: 0.00839

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00582

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

CISD2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.6
DANN	Benign	0.72

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: rs143443440; hg19: chr4-103795697;