rs7535953

chr1-225346646-G-Achr1-225346646-G-Cchr1-225346646-G-T

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.11288G>A(p.Arg3763Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,539,904 control chromosomes in the GnomAD database, including 154,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18352 hom., cov: 31)
  • Exomes 𝑓: 0.44 (136187 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.104

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=1.3200319E-5).
• BP6: Variant 1-225346646-G-A is Benign according to our data. Variant chr1-225346646-G-A is described in ClinVar as [Benign]. Clinvar id is 402660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1	c.11288G>A	p.Arg3763Lys	missense_variant	71/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1	c.11288G>A	p.Arg3763Lys	missense_variant	71/86		NM_001367479.1	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73297 AN: 151754 Hom.: 18321 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.463 AC: 69057 AN: 149002 Hom.: 16279 AF XY: 0.465 AC XY: 36866 AN XY: 79214

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.494

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.496

Gnomad SAS exome AF: 0.550

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.440 AC: 611174 AN: 1388032 Hom.: 136187 Cov.: 32 AF XY: 0.444 AC XY: 303773 AN XY: 684808

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.483 AC: 73375 AN: 151872 Hom.: 18352 Cov.: 31 AF XY: 0.478 AC XY: 35508 AN XY: 74230

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.464

Alfa AF: 0.435 Hom.: 28931

Bravo AF: 0.498

TwinsUK AF: 0.434 AC: 1608

ALSPAC AF: 0.434 AC: 1671

ExAC AF: 0.473 AC: 9945

Asia WGS AF: 0.539 AC: 1871 AN: 3476

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	0.095
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.83
Dann	Benign	0.66
DEOGEN2	Benign	0.0046	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.32	T;T;.
MetaRNN	Benign	0.000013	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.56	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.087	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.013
ClinPred		0.0058	T
GERP RS		-3.8
Varity_R		0.046

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: rs7535953; hg19: chr1-225534348; COSMIC: COSV59893614;