1-224967412-A-T

Variant names:

• chr1-224967412-A-T
• rs2501155
• NM_001367479.1:c.499-19A>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367479.1(DNAH14):​c.499-19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,337,148 control chromosomes in the GnomAD database, including 4,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (3109 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1086 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-224967412-A-T is Benign according to our data. Variant chr1-224967412-A-T is described in ClinVar as [Benign]. Clinvar id is 1174229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.499-19A>T		intron_variant	Intron 5 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.499-19A>T		intron_variant	Intron 5 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22558 AN: 148524 Hom.: 3099 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0199

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.127 AC: 14743 AN: 116138 Hom.: 1017 AF XY: 0.118 AC XY: 7483 AN XY: 63400

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.264

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.0425

Gnomad NFE exome AF: 0.0515

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0519 AC: 61730 AN: 1188530 Hom.: 1086 Cov.: 24 AF XY: 0.0516 AC XY: 30355 AN XY: 588670

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.0680

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.0828

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0342

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome AF: 0.152 AC: 22592 AN: 148618 Hom.: 3109 Cov.: 32 AF XY: 0.152 AC XY: 11013 AN XY: 72506

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.142

Alfa AF: 0.00792 Hom.: 6

Bravo AF: 0.173

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.45

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: rs2501155; hg19: chr1-225155114;