chr1-225305881-G-A

Variant names:

• chr1-225305881-G-A
• rs10495234
• NM_001367479.1:c.9005+792G>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.9005+792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,142 control chromosomes in the GnomAD database, including 7,119 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 0.29 (7119 hom., cov: 33)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.9005+792G>A		intron	N/A	NP_001354408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.9005+792G>A		intron	N/A	ENSP00000508305.1
	DNAH14	ENST00000327794.10	TSL:1	n.2117+792G>A		intron	N/A	ENSP00000328980.6
	DNAH14	ENST00000430092.5	TSL:5	c.8726+792G>A		intron	N/A	ENSP00000414402.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44224 AN: 152022 Hom.: 7111 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.291 AC: 44247 AN: 152142 Hom.: 7119 Cov.: 33 AF XY: 0.296 AC XY: 21996 AN XY: 74384

African (AFR) AF: 0.151 AC: 6291 AN: 41534

American (AMR) AF: 0.359 AC: 5488 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2251 AN: 5174

South Asian (SAS) AF: 0.420 AC: 2026 AN: 4822

European-Finnish (FIN) AF: 0.358 AC: 3790 AN: 10588

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22524 AN: 67968

Other (OTH) AF: 0.295 AC: 622 AN: 2112

Alfa AF: 0.321 Hom.: 4796

Bravo AF: 0.283

Asia WGS AF: 0.426 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10495234; hg19: chr1-225493583;