chr2-68131321-G-T

Position:

• chr2-68131321-G-T

Variant summary

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

The NM_138458.4(DNAAF10):​c.991C>A​(p.Pro331Thr) 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: 31)
• Consequence: DNAAF10 NM_138458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.52

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, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF10	NM_138458.4	c.991C>A	p.Pro331Thr	missense_variant	8/8	ENST00000295121.11	NP_612467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF10	ENST00000295121.11	c.991C>A	p.Pro331Thr	missense_variant	8/8	1	NM_138458.4	ENSP00000295121.6
ENSG00000273398	ENST00000406334.3	n.*1008C>A		non_coding_transcript_exon_variant	15/15	2		ENSP00000384974.3
ENSG00000273398	ENST00000406334.3	n.*1008C>A		3_prime_UTR_variant	15/15	2		ENSP00000384974.3
DNAAF10	ENST00000492039.6	n.981C>A		non_coding_transcript_exon_variant	8/10	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Sep 27, 2022

The c.991C>A (p.P331T) alteration is located in exon 8 (coding exon 8) of the WDR92 gene. This alteration results from a C to A substitution at nucleotide position 991, causing the proline (P) at amino acid position 331 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.072	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.64
Sift	Benign	0.058	T
Sift4G	Benign	0.070	T
Polyphen		0.99	D
Vest4		0.79
MutPred		0.47		Loss of ubiquitination at K333 (P = 0.0718);
MVP		0.36
MPC		0.85
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.59
gMVP		0.64

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: chr2-68358453;