1-225257950-G-T

Variant names:

• chr1-225257950-G-T
• rs670255
• NM_001367479.1:c.6866-10G>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.6866-10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,529,598 control chromosomes in the GnomAD database, including 64,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12768 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51529 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Scores: Splicing: ADA: 0.00001947
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.188
• Publications: 6 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=-0.97).
• BP6: Variant 1-225257950-G-T is Benign according to our data. Variant chr1-225257950-G-T is described in ClinVar as Benign. ClinVar VariationId is 402653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 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.6866-10G>T		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.6866-10G>T		intron	N/A	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000327794.10	TSL:1	n.146-10G>T		intron	N/A	ENSP00000328980.6	H7BXS7
	DNAH14	ENST00000430092.5	TSL:5	c.6848-10G>T		intron	N/A	ENSP00000414402.1	Q0VDD8-4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55491 AN: 151026 Hom.: 12732 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.372

GnomAD2 exomes AF: 0.317 AC: 45596 AN: 143998 AF XY: 0.309

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.616

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.256 AC: 352540 AN: 1378466 Hom.: 51529 Cov.: 30 AF XY: 0.257 AC XY: 174502 AN XY: 679930

African (AFR) AF: 0.636 AC: 19167 AN: 30124

American (AMR) AF: 0.438 AC: 14348 AN: 32792

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 5879 AN: 24588

East Asian (EAS) AF: 0.585 AC: 20404 AN: 34888

South Asian (SAS) AF: 0.348 AC: 26530 AN: 76208

European-Finnish (FIN) AF: 0.201 AC: 9785 AN: 48742

Middle Eastern (MID) AF: 0.239 AC: 1343 AN: 5614

European-Non Finnish (NFE) AF: 0.223 AC: 238525 AN: 1068464

Other (OTH) AF: 0.290 AC: 16559 AN: 57046

GnomAD4 genome AF: 0.368 AC: 55584 AN: 151132 Hom.: 12768 Cov.: 32 AF XY: 0.368 AC XY: 27170 AN XY: 73736

African (AFR) AF: 0.618 AC: 25551 AN: 41320

American (AMR) AF: 0.394 AC: 6002 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 826 AN: 3462

East Asian (EAS) AF: 0.607 AC: 3132 AN: 5164

South Asian (SAS) AF: 0.383 AC: 1840 AN: 4808

European-Finnish (FIN) AF: 0.207 AC: 2085 AN: 10092

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15180 AN: 67766

Other (OTH) AF: 0.372 AC: 779 AN: 2092

Alfa AF: 0.228 Hom.: 2404

Bravo AF: 0.395

Asia WGS AF: 0.508 AC: 1764 AN: 3474

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	-0.97
CADD	Benign	2.9
DANN	Benign	0.18
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs670255; hg19: chr1-225445652;