chr2-68137391-T-C

Position:

• chr2-68137391-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138458.4(DNAAF10):​c.676A>G​(p.Lys226Glu) 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 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: 8.02

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF10	NM_138458.4	c.676A>G	p.Lys226Glu	missense_variant	6/8	ENST00000295121.11	NP_612467.1
DNAAF10	NM_001256476.2	c.676A>G	p.Lys226Glu	missense_variant	6/7		NP_001243405.1
DNAAF10	NR_046234.2	n.647A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF10	ENST00000295121.11	c.676A>G	p.Lys226Glu	missense_variant	6/8	1	NM_138458.4	ENSP00000295121.6
ENSG00000273398	ENST00000406334.3	n.*693A>G		non_coding_transcript_exon_variant	13/15	2		ENSP00000384974.3
ENSG00000273398	ENST00000406334.3	n.*693A>G		3_prime_UTR_variant	13/15	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.676A>G (p.K226E) alteration is located in exon 6 (coding exon 6) of the WDR92 gene. This alteration results from a A to G substitution at nucleotide position 676, causing the lysine (K) at amino acid position 226 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.060	T;.;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Pathogenic	3.4	M;.;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.78
MutPred		0.74		Loss of ubiquitination at K226 (P = 0.021);.;Loss of ubiquitination at K226 (P = 0.021);
MVP		0.41
MPC		1.2
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.75

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: chr2-68364523;