chr2-68157422-G-C

Position:

• chr2-68157422-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000406245.6(DNAAF10):​c.-169C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF10 ENST00000406245.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.16

Genes affected

DNAAF10 (HGNC:25176): (dynein axonemal assembly factor 10) This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ENSG00000273398 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF10	NM_138458.4	c.22C>G	p.Gln8Glu	missense_variant	1/8	ENST00000295121.11	NP_612467.1
DNAAF10	NM_001256476.2	c.22C>G	p.Gln8Glu	missense_variant	1/7		NP_001243405.1
DNAAF10	NR_046234.2	n.106C>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF10	ENST00000295121.11	c.22C>G	p.Gln8Glu	missense_variant	1/8	1	NM_138458.4	ENSP00000295121.6
ENSG00000273398	ENST00000406334.3	n.*39C>G		non_coding_transcript_exon_variant	8/15	2		ENSP00000384974.3
ENSG00000273398	ENST00000406334.3	n.*39C>G		3_prime_UTR_variant	8/15	2		ENSP00000384974.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 14, 2024

The c.22C>G (p.Q8E) alteration is located in exon 1 (coding exon 1) of the WDR92 gene. This alteration results from a C to G substitution at nucleotide position 22, causing the glutamine (Q) at amino acid position 8 to be replaced by a glutamic acid (E). 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	Benign	0.26
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	-0.071	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.57
Sift	Benign	0.039	D;T
Sift4G	Uncertain	0.031	D;D
Polyphen		0.98	D;.
Vest4		0.81
MutPred		0.63		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.24
MPC		0.65
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1673658589; hg19: chr2-68384554;