chr1-225374683-C-T

Variant names:

• chr1-225374683-C-T
• rs10915816
• NM_001367479.1:c.12319-5C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

DNAH14 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.12319-5C>T		splice_region intron	N/A	NP_001354408.1	A0A804HLD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.12319-5C>T		splice_region intron	N/A	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000327794.10	TSL:1	n.*530-5C>T		splice_region intron	N/A	ENSP00000328980.6	H7BXS7
	DNAH14	ENST00000430092.5	TSL:5	c.12040-5C>T		splice_region intron	N/A	ENSP00000414402.1	Q0VDD8-4

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

GnomAD2 exomes AF: 0.812 AC: 123258 AN: 151766 AF XY: 0.806

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 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

African (AFR) AF: 0.433 AC: 13582 AN: 31348

American (AMR) AF: 0.871 AC: 30512 AN: 35050

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 21348 AN: 24842

East Asian (EAS) AF: 0.964 AC: 34341 AN: 35628

South Asian (SAS) AF: 0.694 AC: 53966 AN: 77774

European-Finnish (FIN) AF: 0.859 AC: 42058 AN: 48988

Middle Eastern (MID) AF: 0.859 AC: 4846 AN: 5642

European-Non Finnish (NFE) AF: 0.835 AC: 894745 AN: 1071584

Other (OTH) AF: 0.821 AC: 47159 AN: 57458

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

African (AFR) AF: 0.452 AC: 18704 AN: 41418

American (AMR) AF: 0.861 AC: 13172 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2957 AN: 3468

East Asian (EAS) AF: 0.957 AC: 4949 AN: 5174

South Asian (SAS) AF: 0.694 AC: 3346 AN: 4822

European-Finnish (FIN) AF: 0.862 AC: 9131 AN: 10594

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57100 AN: 67984

Other (OTH) AF: 0.790 AC: 1666 AN: 2110

Alfa AF: 0.814 Hom.: 79439

Bravo AF: 0.727

Asia WGS AF: 0.821 AC: 2854 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.53
PhyloP100		-2.4
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10915816; hg19: chr1-225562385;