Variant rs63749888 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001008388.5(CISD2):c.109G>C(p.Glu37Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CISD2
NM_001008388.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.45

Variant links:

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]

CISD2 links:

SLC9B1 (HGNC:24244): (solute carrier family 9 member B1) The protein encoded by this gene is a sodium/hydrogen exchanger and transmembrane protein. Highly conserved orthologs of this gene have been found in other mammalian species. The expression of this gene may be limited to testis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

SLC9B1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-102885221-G-C is Pathogenic according to our data. Variant chr4-102885221-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 892.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-102885221-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CISD2	NM_001008388.5 linkuse as main transcript	c.109G>C	p.Glu37Gln	missense_variant	2/3	ENST00000273986.10	NP_001008389.1
SLC9B1	NM_001100874.3 linkuse as main transcript	c.*12C>G		3_prime_UTR_variant	12/12		NP_001094344.2
SLC9B1	NR_047513.2 linkuse as main transcript	n.1420C>G		non_coding_transcript_exon_variant	11/11
SLC9B1	NR_047515.2 linkuse as main transcript	n.1282C>G		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CISD2	ENST00000273986.10 linkuse as main transcript	c.109G>C	p.Glu37Gln	missense_variant	2/3	1	NM_001008388.5	ENSP00000273986	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727086

show subpopulations

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:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Wolfram syndrome 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

A;A;A

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

N;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.11

T;.;D

Sift4G

Benign

0.25

T;.;T

Polyphen

1.0

D;D;.

Vest4

0.68

MutPred

0.73

Gain of MoRF binding (P = 0.0658);Gain of MoRF binding (P = 0.0658);.;

MVP

0.48

MPC

1.7

ClinPred

0.78

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.82

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.82

Position offset: -5

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

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