rs10495237

Variant names:

• chr1-225318592-A-G
• rs10495237
• NM_001367479.1:c.9250A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367479.1(DNAH14):​c.9250A>G​(p.Asn3084Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,544,522 control chromosomes in the GnomAD database, including 7,772 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N3084S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.11 (1181 hom., cov: 32)
  • Exomes 𝑓: 0.084 (6591 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.879
• Publications: 18 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031424463).
• BP6: Variant 1-225318592-A-G is Benign according to our data. Variant chr1-225318592-A-G is described in ClinVar as Benign. ClinVar VariationId is 402655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.9250A>G	p.Asn3084Asp	missense	Exon 61 of 86	NP_001354408.1	A0A804HLD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.9250A>G	p.Asn3084Asp	missense	Exon 61 of 86	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000327794.10	TSL:1	n.2362A>G		non_coding_transcript_exon	Exon 18 of 40	ENSP00000328980.6	H7BXS7
	DNAH14	ENST00000430092.5	TSL:5	c.8971A>G	p.Asn2991Asp	missense	Exon 59 of 84	ENSP00000414402.1	Q0VDD8-4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17207 AN: 152114 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.119 AC: 18148 AN: 152648 AF XY: 0.111

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.0468

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.0707

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0844 AC: 117578 AN: 1392288 Hom.: 6591 Cov.: 31 AF XY: 0.0837 AC XY: 57447 AN XY: 686304

African (AFR) AF: 0.145 AC: 4541 AN: 31410

American (AMR) AF: 0.214 AC: 7419 AN: 34666

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 1201 AN: 25092

East Asian (EAS) AF: 0.291 AC: 10340 AN: 35552

South Asian (SAS) AF: 0.0740 AC: 5713 AN: 77172

European-Finnish (FIN) AF: 0.135 AC: 6633 AN: 49274

Middle Eastern (MID) AF: 0.0480 AC: 273 AN: 5688

European-Non Finnish (NFE) AF: 0.0708 AC: 76122 AN: 1075618

Other (OTH) AF: 0.0923 AC: 5336 AN: 57816

GnomAD4 genome AF: 0.113 AC: 17230 AN: 152234 Hom.: 1181 Cov.: 32 AF XY: 0.119 AC XY: 8821 AN XY: 74436

African (AFR) AF: 0.142 AC: 5911 AN: 41540

American (AMR) AF: 0.166 AC: 2532 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5168

South Asian (SAS) AF: 0.0879 AC: 423 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1469 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5065 AN: 68024

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.0849 Hom.: 2236

Bravo AF: 0.117

TwinsUK AF: 0.0704 AC: 261

ALSPAC AF: 0.0675 AC: 260

ESP6500AA AF: 0.153 AC: 212

ESP6500EA AF: 0.0669 AC: 213

ExAC AF: 0.0849 AC: 2113

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.88
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.0070
Sift	Benign	0.52	T
Sift4G	Benign	0.19	T
Polyphen		0.038	B
Vest4		0.15
ClinPred		0.0032	T
GERP RS		1.5
Varity_R		0.057
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: rs10495237; hg19: chr1-225506294; COSMIC: COSV59895699;