rs2290981

chr15-55467490-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF4	NM_130810.4	c.406-329C>T		intron_variant		ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1	n.661-329C>T		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.406-329C>T		intron_variant
DNAAF4	NM_001033560.2	c.406-329C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7	c.406-329C>T		intron_variant		1	NM_130810.4	P1

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

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0482

Gnomad4 ASJ AF: 0.0641

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0587

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0487 Hom.: 35

Bravo AF: 0.0478

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.34
Dann	Benign	0.18

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: rs2290981; hg19: chr15-55759688;