rs10495237

chr1-225318592-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 12/16 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, single submitter B:1
• Conservation: PhyloP100: 0.879

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 Benign. Variant got -14 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 id is 402655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1	c.9250A>G	p.Asn3084Asp	missense_variant	61/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1	c.9250A>G	p.Asn3084Asp	missense_variant	61/86		NM_001367479.1	P1

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

GnomAD3 exomes AF: 0.119 AC: 18148 AN: 152648 Hom.: 1547 AF XY: 0.111 AC XY: 8963 AN XY: 80572

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 SAS exome AF: 0.0757

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.0479

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0708

Gnomad4 OTH exome AF: 0.0923

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0767 Hom.: 856

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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;T;.
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.038	.;B;B
Vest4		0.15
ClinPred		0.0032	T
GERP RS		1.5
Varity_R		0.057

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: rs10495237; hg19: chr1-225506294; COSMIC: COSV59895699;