Variant rs879253737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate

The NM_018063.5(HELLS):c.2400_2402del(p.Leu801del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000688 in 1,598,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

HELLS
NM_018063.5 inframe_deletion

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.60

Variant links:

Genes affected

HELLS (HGNC:4861): (helicase, lymphoid specific) This gene encodes a lymphoid-specific helicase. Other helicases function in processes involving DNA strand separation, including replication, repair, recombination, and transcription. This protein is thought to be involved with cellular proliferation and may play a role in leukemogenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2014]

HELLS links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_018063.5. Strenght limited to Supporting due to length of the change: 1aa.

PP5

Variant 10-94597082-AGTT-A is Pathogenic according to our data. Variant chr10-94597082-AGTT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225528.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-94597082-AGTT-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELLS	NM_018063.5 linkuse as main transcript	c.2400_2402del	p.Leu801del	inframe_deletion	21/22	ENST00000348459.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELLS	ENST00000348459.10 linkuse as main transcript	c.2400_2402del	p.Leu801del	inframe_deletion	21/22	1	NM_018063.5	P1	Q9NRZ9-1
	ENST00000432120.1 linkuse as main transcript	n.208-13712_208-13710del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249770

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000691

AC:

AN:

1446562

Hom.:

AF XY:

0.00000694

AC XY:

AN XY:

720522

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 4

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 19, 2017

- -

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Invitae

Jul 15, 2022

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 225528). This variant has been observed in individual(s) with Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome (PMID: 26216346, 30511102). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs767250687, gnomAD 0.009%). This variant, c.2400_2402del, results in the deletion of 1 amino acid(s) of the HELLS protein (p.Leu801del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Other links and lift over