2-68134775-C-T

Variant names:

• chr2-68134775-C-T
• NM_138458.4:c.793G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138458.4(DNAAF10):​c.793G>A​(p.Val265Ile) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF10 NM_138458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31919312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF10	NM_138458.4	c.793G>A	p.Val265Ile	missense_variant	Exon 7 of 8	ENST00000295121.11	NP_612467.1
DNAAF10	NM_001256476.2	c.793G>A	p.Val265Ile	missense_variant	Exon 7 of 7		NP_001243405.1
DNAAF10	NR_046234.2	n.764G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF10	ENST00000295121.11	c.793G>A	p.Val265Ile	missense_variant	Exon 7 of 8	1	NM_138458.4	ENSP00000295121.6
ENSG00000273398	ENST00000406334.3	n.*810G>A		non_coding_transcript_exon_variant	Exon 14 of 15	2		ENSP00000384974.3
ENSG00000273398	ENST00000406334.3	n.*810G>A		3_prime_UTR_variant	Exon 14 of 15	2		ENSP00000384974.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.793G>A (p.V265I) alteration is located in exon 7 (coding exon 7) of the WDR92 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the valine (V) at amino acid position 265 to be replaced by an isoleucine (I). 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	0.16
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0057	T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	2.9	M;.;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.95	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.021	D;D;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.59	P;.;.
Vest4		0.55
MutPred		0.31		Gain of catalytic residue at V265 (P = 0.078);.;Gain of catalytic residue at V265 (P = 0.078);
MVP		0.41
MPC		0.30
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.096

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: chr2-68361907;