20-38969189-A-G

Position:

• chr20-38969189-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021931.4(DHX35):​c.149A>G​(p.Gln50Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DHX35 NM_021931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.41

Genes affected

DHX35 (HGNC:15861): (DEAH-box helicase 35) DEAD box proteins characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The function of this gene product which is a member of this family, has not been determined. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2010]

DHX35 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX35	NM_021931.4	c.149A>G	p.Gln50Arg	missense_variant	2/22	ENST00000252011.8	NP_068750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX35	ENST00000252011.8	c.149A>G	p.Gln50Arg	missense_variant	2/22	1	NM_021931.4	ENSP00000252011.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.149A>G (p.Q50R) alteration is located in exon 2 (coding exon 2) of the DHX35 gene. This alteration results from a A to G substitution at nucleotide position 149, causing the glutamine (Q) at amino acid position 50 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.049	D;D;D
Sift4G	Benign	0.070	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.79
MutPred		0.30		Gain of MoRF binding (P = 0.0297);Gain of MoRF binding (P = 0.0297);Gain of MoRF binding (P = 0.0297);
MVP		0.52
MPC		0.69
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.54
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-37597832;