1-225053392-C-G

Variant names:

• chr1-225053392-C-G
• rs12038394
• NM_001367479.1:c.2424+1597C>G

Variant summary

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

The NM_001367479.1(DNAH14):​c.2424+1597C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,042 control chromosomes in the GnomAD database, including 10,125 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 0.33 (10125 hom., cov: 32)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.2424+1597C>G		intron_variant	Intron 17 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.2424+1597C>G		intron_variant	Intron 17 of 85		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.2424+1597C>G		intron_variant	Intron 17 of 83	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.2424+1597C>G		intron_variant	Intron 16 of 82	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.2226+1708C>G		intron_variant	Intron 13 of 60	5		ENSP00000409472.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50796 AN: 151924 Hom.: 10117 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.334 AC: 50807 AN: 152042 Hom.: 10125 Cov.: 32 AF XY: 0.337 AC XY: 25006 AN XY: 74300

African (AFR) AF: 0.108 AC: 4474 AN: 41502

American (AMR) AF: 0.390 AC: 5945 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2773 AN: 5140

South Asian (SAS) AF: 0.453 AC: 2185 AN: 4820

European-Finnish (FIN) AF: 0.410 AC: 4330 AN: 10554

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28671 AN: 67984

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.252 Hom.: 677

Bravo AF: 0.324

Asia WGS AF: 0.486 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.29
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: rs12038394; hg19: chr1-225241094;