rs201634729

Variant names:

• chr1-224952769-A-G
• rs201634729
• NM_001367479.1:c.67A>G

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.67A>G​(p.Thr23Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 1,597,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.124
• Publications: 0 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
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

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 (MetaRNN=0.039163083).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.67A>G	p.Thr23Ala	missense	Exon 2 of 86	NP_001354408.1	A0A804HLD3
	DNAH14	NM_001145154.3		c.67A>G	p.Thr23Ala	missense	Exon 2 of 11	NP_001138626.1	Q0VDD8-2
	DNAH14	NM_001349911.2		c.67A>G	p.Thr23Ala	missense	Exon 2 of 11	NP_001336840.1	M9MMK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.67A>G	p.Thr23Ala	missense	Exon 2 of 86	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000400952.7	TSL:1	c.67A>G	p.Thr23Ala	missense	Exon 2 of 11	ENSP00000383737.3	Q0VDD8-2
	DNAH14	ENST00000366849.5	TSL:1	c.67A>G	p.Thr23Ala	missense	Exon 2 of 11	ENSP00000355814.1	M9MMK7

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000133 AC: 3 AN: 226016 AF XY: 0.00000818

Gnomad AFR exome AF: 0.000146

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000998

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000415 AC: 6 AN: 1445574 Hom.: 0 Cov.: 29 AF XY: 0.00000418 AC XY: 3 AN XY: 717998

African (AFR) AF: 0.0000915 AC: 3 AN: 32788

American (AMR) AF: 0.00 AC: 0 AN: 42710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 39308

South Asian (SAS) AF: 0.00 AC: 0 AN: 83540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103534

Other (OTH) AF: 0.0000168 AC: 1 AN: 59626

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.000121 AC: 5 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000277 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000829 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.3
DANN	Benign	0.62
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.12
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.080
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.27
MVP		0.081
MPC		0.051
ClinPred		0.012	T
GERP RS		-4.5
PromoterAI		-0.011	Neutral
Varity_R		0.038
gMVP		0.014
Mutation Taster		=94/6	polymorphism

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: rs201634729; hg19: chr1-225140471;