rs3128651

chr1-225080641-A-Gchr1-225080641-A-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.3029A>G(p.Lys1010Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,551,318 control chromosomes in the GnomAD database, including 663,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (51631 hom., cov: 33)
  • Exomes 𝑓: 0.93 (612260 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.598

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=1.9215813E-6).
• BP6: Variant 1-225080641-A-G is Benign according to our data. Variant chr1-225080641-A-G is described in ClinVar as [Benign]. Clinvar id is 402647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1	c.3029A>G	p.Lys1010Arg	missense_variant	19/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1	c.3029A>G	p.Lys1010Arg	missense_variant	19/86		NM_001367479.1	P1
DNAH14	ENST00000430092.5	c.3029A>G	p.Lys1010Arg	missense_variant	19/84	5
DNAH14	ENST00000439375.6	c.3029A>G	p.Lys1010Arg	missense_variant	18/83	5
DNAH14	ENST00000445597.6	c.2831A>G	p.Lys944Arg	missense_variant	15/61	5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121026 AN: 151772 Hom.: 51613 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.822

GnomAD3 exomes AF: 0.870 AC: 137039 AN: 157606 Hom.: 60968 AF XY: 0.879 AC XY: 73173 AN XY: 83214

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.928

Gnomad EAS exome AF: 0.702

Gnomad SAS exome AF: 0.869

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.891

GnomAD4 exome AF: 0.931 AC: 1302573 AN: 1399428 Hom.: 612260 Cov.: 57 AF XY: 0.931 AC XY: 642580 AN XY: 690206

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.926

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.869

Gnomad4 FIN exome AF: 0.968

Gnomad4 NFE exome AF: 0.962

Gnomad4 OTH exome AF: 0.894

GnomAD4 genome AF: 0.797 AC: 121080 AN: 151890 Hom.: 51631 Cov.: 33 AF XY: 0.797 AC XY: 59182 AN XY: 74244

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.823

Alfa AF: 0.929 Hom.: 150550

Bravo AF: 0.769

TwinsUK AF: 0.960 AC: 3560

ALSPAC AF: 0.955 AC: 3679

ESP6500AA AF: 0.519 AC: 718

ESP6500EA AF: 0.961 AC: 3057

ExAC AF: 0.859 AC: 21026

Asia WGS AF: 0.753 AC: 2622 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	0.068
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.26
Dann	Benign	0.89
DEOGEN2	Benign	0.0015	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.24	T;T;.
MetaRNN	Benign	0.0000019	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.050	N;N;N
REVEL	Benign	0.033
Sift	Benign	0.74	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.10
ClinPred		0.00057	T
GERP RS		3.2
Varity_R		0.026

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: rs3128651; hg19: chr1-225268343; COSMIC: COSV60741180;