chr8-132572321-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_012472.6(DNAAF11):​c.1386G>A​(p.Val462Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAAF11 NM_012472.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 8-132572321-C-T is Benign according to our data. Variant chr8-132572321-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3020919.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Val462Val	synonymous	Exon 12 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.1326G>A	p.Val442Val	synonymous	Exon 11 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.1140G>A	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>A	p.Val462Val	synonymous	Exon 12 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000519595.5	TSL:1	c.1386G>A	p.Val462Val	synonymous	Exon 12 of 12	ENSP00000429791.1	Q86X45-1
	DNAAF11	ENST00000250173.5	TSL:1	c.*250G>A		3_prime_UTR	Exon 13 of 13	ENSP00000250173.2	G5EA20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459622 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726168

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111222

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.3
DANN	Benign	0.54
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;