rs12742757

Positions:

• chr1-225346029-T-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001367479.1(DNAH14):​c.10746T>A​(p.Ile3582=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 1,551,380 control chromosomes in the GnomAD database, including 7,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1173 hom., cov: 32)
  • Exomes 𝑓: 0.085 (6551 hom.)
• Consequence: DNAH14 NM_001367479.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.813

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-225346029-T-A is Benign according to our data. Variant chr1-225346029-T-A is described in ClinVar as [Benign]. Clinvar id is 402658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.813 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1	c.10746T>A	p.Ile3582=	synonymous_variant	70/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1	c.10746T>A	p.Ile3582=	synonymous_variant	70/86		NM_001367479.1	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17255 AN: 151948 Hom.: 1170 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.120 AC: 18615 AN: 155208 Hom.: 1588 AF XY: 0.112 AC XY: 9217 AN XY: 82312

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.0478

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.0751

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.0709

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0848 AC: 118628 AN: 1399316 Hom.: 6551 Cov.: 42 AF XY: 0.0841 AC XY: 58012 AN XY: 690176

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.0485

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.0745

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0713

Gnomad4 OTH exome AF: 0.0929

GnomAD4 genome AF: 0.114 AC: 17275 AN: 152064 Hom.: 1173 Cov.: 32 AF XY: 0.119 AC XY: 8819 AN XY: 74346

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0832 Hom.: 213

Bravo AF: 0.118

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.2
DANN	Benign	0.68

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: rs12742757; hg19: chr1-225533731; COSMIC: COSV59895710;