rs7527925

chr1-225346517-T-C

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.11159T>C(p.Val3720Ala) 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 1,550,514 control chromosomes in the GnomAD database, including 155,798 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 (18351 hom., cov: 32)
  • Exomes 𝑓: 0.44 (137447 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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=1.0780426E-5).
• BP6: Variant 1-225346517-T-C is Benign according to our data. Variant chr1-225346517-T-C is described in ClinVar as [Benign]. Clinvar id is 402659.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.11159T>C	p.Val3720Ala	missense_variant	71/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1	c.11159T>C	p.Val3720Ala	missense_variant	71/86		NM_001367479.1	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73287 AN: 151852 Hom.: 18320 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.460 AC: 70697 AN: 153598 Hom.: 16665 AF XY: 0.463 AC XY: 37714 AN XY: 81534

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.493

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.441 AC: 616401 AN: 1398544 Hom.: 137447 Cov.: 42 AF XY: 0.444 AC XY: 306202 AN XY: 689822

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.483 AC: 73365 AN: 151970 Hom.: 18351 Cov.: 32 AF XY: 0.478 AC XY: 35498 AN XY: 74282

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.464

Alfa AF: 0.435 Hom.: 37889

Bravo AF: 0.498

TwinsUK AF: 0.435 AC: 1613

ALSPAC AF: 0.435 AC: 1675

ESP6500AA AF: 0.608 AC: 842

ESP6500EA AF: 0.442 AC: 1404

ExAC AF: 0.476 AC: 10017

Asia WGS AF: 0.539 AC: 1868 AN: 3468

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	0.052
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	12
Dann	Benign	0.59
DEOGEN2	Benign	0.0020	T;.;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.086	T;T;.
MetaRNN	Benign	0.000011	T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.54	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.75	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.057
ClinPred		0.00093	T
GERP RS		3.5
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: rs7527925; hg19: chr1-225534219; COSMIC: COSV100586726;