chr1-225122468-G-A

Variant names:

• chr1-225122468-G-A
• rs6686694
• NM_001367479.1:c.4167-1059G>A

Variant summary

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

The NM_001367479.1(DNAH14):​c.4167-1059G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,926 control chromosomes in the GnomAD database, including 13,839 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 0.32 (13839 hom., cov: 32)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 2 publications found

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.4167-1059G>A		intron_variant	Intron 26 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.4167-1059G>A		intron_variant	Intron 26 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48829 AN: 151808 Hom.: 13787 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.322 AC: 48935 AN: 151926 Hom.: 13839 Cov.: 32 AF XY: 0.320 AC XY: 23753 AN XY: 74244

African (AFR) AF: 0.762 AC: 31568 AN: 41402

American (AMR) AF: 0.266 AC: 4057 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1580 AN: 5152

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4810

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8039 AN: 67958

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.212 Hom.: 1572

Bravo AF: 0.352

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.40
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: rs6686694; hg19: chr1-225310170;