rs2501107

Variant names:

• chr1-225042906-C-A
• rs2501107
• NM_001367479.1:c.1560C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225042906-C-A
• chr1-225042906-C-G
• chr1-225042906-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001367479.1(DNAH14):​c.1560C>A​(p.Cys520*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C520C) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAH14 NM_001367479.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.1560C>A	p.Cys520*	stop_gained	Exon 13 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.1560C>A	p.Cys520*	stop_gained	Exon 13 of 86		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.1560C>A	p.Cys520*	stop_gained	Exon 13 of 84	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.1560C>A	p.Cys520*	stop_gained	Exon 12 of 83	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.1617C>A	p.Cys539*	stop_gained	Exon 11 of 61	5		ENSP00000409472.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Benign	-0.082
FATHMM_MKL	Benign	0.041	N
Vest4		0.048
GERP RS		-0.88

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: rs2501107; hg19: chr1-225230608;