8-132572321-C-G

Variant names:

• chr8-132572321-C-G
• rs749984059
• NM_012472.6:c.1386G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012472.6(DNAAF11):​c.1386G>C​(p.Val462Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V462V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF11 NM_012472.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 0 publications found

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]

DNAAF11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.446 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012472.6. 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
	DNAAF11	NM_012472.6	MANE Select	c.1386G>C	p.Val462Val	synonymous	Exon 12 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.1326G>C	p.Val442Val	synonymous	Exon 11 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.1140G>C	p.Val380Val	synonymous	Exon 10 of 10	NP_001308891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.1386G>C	p.Val462Val	synonymous	Exon 12 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000519595.5	TSL:1	c.1386G>C	p.Val462Val	synonymous	Exon 12 of 12	ENSP00000429791.1	Q86X45-1
	DNAAF11	ENST00000250173.5	TSL:1	c.*250G>C		3_prime_UTR	Exon 13 of 13	ENSP00000250173.2	G5EA20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248704 AF XY: 0.00000744

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		-0.45

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: rs749984059; hg19: chr8-133584569;