chr2-68134771-C-G

Variant names:

• chr2-68134771-C-G
• rs1007173839
• NM_138458.4:c.797G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138458.4(DNAAF10):​c.797G>C​(p.Arg266Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,034 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R266Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAAF10 NM_138458.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF10	NM_138458.4	MANE Select	c.797G>C	p.Arg266Pro	missense	Exon 7 of 8	NP_612467.1	Q96MX6-1
	DNAAF10	NM_001256476.2		c.797G>C	p.Arg266Pro	missense	Exon 7 of 7	NP_001243405.1	Q96MX6-2
	DNAAF10	NR_046234.2		n.768G>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF10	ENST00000295121.11	TSL:1 MANE Select	c.797G>C	p.Arg266Pro	missense	Exon 7 of 8	ENSP00000295121.6	Q96MX6-1
	DNAAF10	ENST00000409164.1	TSL:1	c.797G>C	p.Arg266Pro	missense	Exon 7 of 7	ENSP00000386746.1	Q96MX6-2
	DNAAF10	ENST00000406245.6	TSL:1	c.494G>C	p.Arg165Pro	missense	Exon 7 of 7	ENSP00000384518.2	Q8ND98

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459034 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725852

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33276

American (AMR) AF: 0.00 AC: 0 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111486

Other (OTH) AF: 0.00 AC: 0 AN: 60158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.62		Loss of MoRF binding (P = 0.0012)
MVP		0.79
MPC		1.1
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.90
gMVP		0.88
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs1007173839; hg19: chr2-68361903;