rs879253733

Positions:

• chr10-94594702-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_018063.5(HELLS):​c.2096A>G​(p.Gln699Arg) variant causes a missense change involving the alteration of a 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HELLS NM_018063.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.29

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]

ENSG00000244332 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953
• PP5: Variant 10-94594702-A-G is Pathogenic according to our data. Variant chr10-94594702-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 225523.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-94594702-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELLS	NM_018063.5	c.2096A>G	p.Gln699Arg	missense_variant	19/22	ENST00000348459.10	NP_060533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELLS	ENST00000348459.10	c.2096A>G	p.Gln699Arg	missense_variant	19/22	1	NM_018063.5	ENSP00000239027.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 10, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;T;D;.;.;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.8	.;.;H;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	.;.;D;.;D;D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	.;.;D;.;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D
Polyphen		1.0, 1.0	.;.;D;.;D;.
Vest4		0.93
MutPred		0.80		.;.;Gain of catalytic residue at Q699 (P = 0.1228);.;.;.;
MVP		0.90
MPC		1.7
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.80
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs879253733; hg19: chr10-96354459;