1-225374683-C-T

Variant names:

• chr1-225374683-C-T
• rs10915816
• NM_001367479.1:c.12319-5C>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.12319-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,540,378 control chromosomes in the GnomAD database, including 518,046 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43761 hom., cov: 31)
  • Exomes 𝑓: 0.82 (474285 hom.)
• Consequence: DNAH14 NM_001367479.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002266
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.41

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=-0.88).
• BP6: Variant 1-225374683-C-T is Benign according to our data. Variant chr1-225374683-C-T is described in ClinVar as [Benign]. Clinvar id is 402663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.12319-5C>T		splice_region_variant, intron_variant	Intron 77 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.12319-5C>T		splice_region_variant, intron_variant	Intron 77 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111921 AN: 151946 Hom.: 43744 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.786

GnomAD3 exomes AF: 0.812 AC: 123258 AN: 151766 Hom.: 51071 AF XY: 0.806 AC XY: 64949 AN XY: 80568

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.871

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.954

Gnomad SAS exome AF: 0.694

Gnomad FIN exome AF: 0.856

Gnomad NFE exome AF: 0.836

Gnomad OTH exome AF: 0.849

GnomAD4 exome AF: 0.823 AC: 1142557 AN: 1388314 Hom.: 474285 Cov.: 36 AF XY: 0.820 AC XY: 561059 AN XY: 683934

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.871

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.859

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.736 AC: 111977 AN: 152064 Hom.: 43761 Cov.: 31 AF XY: 0.738 AC XY: 54864 AN XY: 74334

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.790

Alfa AF: 0.823 Hom.: 65648

Bravo AF: 0.727

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.040		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: rs10915816; hg19: chr1-225562385;