NM_001367479.1:c.8272-41A>T

Variant names:

• chr1-225289844-A-T
• rs12042076
• NM_001367479.1:c.8272-41A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367479.1(DNAH14):​c.8272-41A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,098,344 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.8272-41A>T		intron_variant	Intron 54 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.8272-41A>T		intron_variant	Intron 54 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000637 AC: 7 AN: 1098344 Hom.: 0 Cov.: 18 AF XY: 0.00000764 AC XY: 4 AN XY: 523686

African (AFR) AF: 0.00 AC: 0 AN: 23198

American (AMR) AF: 0.0000940 AC: 1 AN: 10642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15518

East Asian (EAS) AF: 0.00 AC: 0 AN: 27880

South Asian (SAS) AF: 0.00 AC: 0 AN: 24530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4166

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 910316

Other (OTH) AF: 0.0000906 AC: 4 AN: 44140

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 34009

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.25
DANN	Benign	0.57
PhyloP100		-0.33

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: rs12042076; hg19: chr1-225477546;