15-55447640-T-C

Variant names:

• chr15-55447640-T-C
• rs622097
• NM_130810.4:c.783+2582A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130810.4(DNAAF4):​c.783+2582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 148,018 control chromosomes in the GnomAD database, including 37,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (37282 hom., cov: 22)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 3 publications found

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130810.4. 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
	DNAAF4	NM_130810.4	MANE Select	c.783+2582A>G		intron	N/A	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033560.2		c.783+2582A>G		intron	N/A	NP_001028732.1	Q8WXU2-2
	DNAAF4	NM_001033559.3		c.783+2582A>G		intron	N/A	NP_001028731.1	Q8WXU2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000321149.7	TSL:1 MANE Select	c.783+2582A>G		intron	N/A	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000448430.6	TSL:1	c.783+2582A>G		intron	N/A	ENSP00000403412.2	Q8WXU2-2
	DNAAF4	ENST00000457155.6	TSL:1	c.783+2582A>G		intron	N/A	ENSP00000402640.2	Q8WXU2-3

Frequencies

GnomAD3 genomes AF: 0.705 AC: 104339 AN: 147898 Hom.: 37247 Cov.: 22

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.716

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.706 AC: 104428 AN: 148018 Hom.: 37282 Cov.: 22 AF XY: 0.709 AC XY: 51066 AN XY: 71978

African (AFR) AF: 0.732 AC: 29306 AN: 40024

American (AMR) AF: 0.772 AC: 11395 AN: 14754

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2578 AN: 3444

East Asian (EAS) AF: 0.902 AC: 4380 AN: 4858

South Asian (SAS) AF: 0.800 AC: 3621 AN: 4528

European-Finnish (FIN) AF: 0.679 AC: 6805 AN: 10026

Middle Eastern (MID) AF: 0.703 AC: 201 AN: 286

European-Non Finnish (NFE) AF: 0.658 AC: 44180 AN: 67144

Other (OTH) AF: 0.719 AC: 1482 AN: 2060

Alfa AF: 0.667 Hom.: 4029

Bravo AF: 0.716

Asia WGS AF: 0.837 AC: 2905 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.16
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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: rs622097; hg19: chr15-55739838;