8-132625413-G-C

Position:

• chr8-132625413-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012472.6(DNAAF11):​c.695C>G​(p.Thr232Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. T232I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF11 NM_012472.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033634096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF11	NM_012472.6	c.695C>G	p.Thr232Arg	missense_variant	6/12	ENST00000620350.5	NP_036604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5	c.695C>G	p.Thr232Arg	missense_variant	6/12	1	NM_012472.6	ENSP00000484634.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249622 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0020
DANN	Benign	0.29
DEOGEN2	Benign	0.0034	.;T;T;T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.19	T;T;.;.;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.034	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.35	.;.;N;N;N
REVEL	Benign	0.0090
Sift	Benign	0.52	.;.;T;T;T
Sift4G	Benign	0.52	T;T;T;T;T
Polyphen		0.014	.;B;B;.;.
Vest4		0.066
MutPred		0.22		Loss of phosphorylation at T232 (P = 0.0165);Loss of phosphorylation at T232 (P = 0.0165);Loss of phosphorylation at T232 (P = 0.0165);Loss of phosphorylation at T232 (P = 0.0165);Loss of phosphorylation at T232 (P = 0.0165);
MVP		0.048
MPC		0.078
ClinPred		0.031	T
GERP RS		-9.6
Varity_R		0.053
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs2293979; hg19: chr8-133637659;