rs12024361

Variant names:

• chr1-225289789-C-T
• rs12024361
• NM_001367479.1:c.8272-96C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367479.1(DNAH14):​c.8272-96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 833,904 control chromosomes in the GnomAD database, including 51,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8138 hom., cov: 32)
  • Exomes 𝑓: 0.35 (43199 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.8272-96C>T		intron	N/A	NP_001354408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.8272-96C>T		intron	N/A	ENSP00000508305.1
	DNAH14	ENST00000327794.10	TSL:1	n.1384-96C>T		intron	N/A	ENSP00000328980.6
	DNAH14	ENST00000430092.5	TSL:5	c.7993-96C>T		intron	N/A	ENSP00000414402.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47136 AN: 151758 Hom.: 8132 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.350 AC: 238790 AN: 682028 Hom.: 43199 AF XY: 0.352 AC XY: 116810 AN XY: 332222

African (AFR) AF: 0.143 AC: 2142 AN: 15012

American (AMR) AF: 0.386 AC: 3607 AN: 9352

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 4056 AN: 12116

East Asian (EAS) AF: 0.481 AC: 12086 AN: 25112

South Asian (SAS) AF: 0.423 AC: 5282 AN: 12488

European-Finnish (FIN) AF: 0.390 AC: 14351 AN: 36804

Middle Eastern (MID) AF: 0.258 AC: 562 AN: 2178

European-Non Finnish (NFE) AF: 0.346 AC: 186566 AN: 538856

Other (OTH) AF: 0.337 AC: 10138 AN: 30110

GnomAD4 genome AF: 0.310 AC: 47155 AN: 151876 Hom.: 8138 Cov.: 32 AF XY: 0.315 AC XY: 23373 AN XY: 74242

African (AFR) AF: 0.156 AC: 6460 AN: 41454

American (AMR) AF: 0.377 AC: 5749 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3464

East Asian (EAS) AF: 0.445 AC: 2298 AN: 5160

South Asian (SAS) AF: 0.440 AC: 2124 AN: 4830

European-Finnish (FIN) AF: 0.375 AC: 3948 AN: 10532

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24358 AN: 67886

Other (OTH) AF: 0.314 AC: 661 AN: 2108

Alfa AF: 0.323 Hom.: 1344

Bravo AF: 0.303

Asia WGS AF: 0.449 AC: 1561 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12024361; hg19: chr1-225477491;