rs2290981

Variant names:

• chr15-55467490-G-A
• rs2290981
• NM_130810.4:c.406-329C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130810.4(DNAAF4):​c.406-329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 151,792 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (266 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-55467490-G-A is Benign according to our data. Variant chr15-55467490-G-A is described in ClinVar as Benign. ClinVar VariationId is 1267505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 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.406-329C>T		intron	N/A	NP_570722.2	Q8WXU2-1
	DNAAF4	NM_001033560.2		c.406-329C>T		intron	N/A	NP_001028732.1	Q8WXU2-2
	DNAAF4	NM_001033559.3		c.406-329C>T		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.406-329C>T		intron	N/A	ENSP00000323275.3	Q8WXU2-1
	DNAAF4	ENST00000448430.6	TSL:1	c.406-329C>T		intron	N/A	ENSP00000403412.2	Q8WXU2-2
	DNAAF4	ENST00000457155.6	TSL:1	c.406-329C>T		intron	N/A	ENSP00000402640.2	Q8WXU2-3

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7605 AN: 151674 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0504

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

GnomAD4 genome AF: 0.0501 AC: 7600 AN: 151792 Hom.: 266 Cov.: 32 AF XY: 0.0501 AC XY: 3717 AN XY: 74172

African (AFR) AF: 0.0165 AC: 684 AN: 41434

American (AMR) AF: 0.0482 AC: 732 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 222 AN: 3466

East Asian (EAS) AF: 0.147 AC: 756 AN: 5138

South Asian (SAS) AF: 0.141 AC: 680 AN: 4808

European-Finnish (FIN) AF: 0.0341 AC: 358 AN: 10512

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0587 AC: 3987 AN: 67930

Other (OTH) AF: 0.0522 AC: 110 AN: 2106

Alfa AF: 0.0481 Hom.: 36

Bravo AF: 0.0478

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.18
PhyloP100		-0.16
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: rs2290981; hg19: chr15-55759688;