1-225367810-C-T

Variant names:

• chr1-225367810-C-T
• rs11578981
• NM_001367479.1:c.12096C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001367479.1(DNAH14):​c.12096C>T​(p.Ala4032Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,545,532 control chromosomes in the GnomAD database, including 213,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16717 hom., cov: 32)
  • Exomes 𝑓: 0.52 (196709 hom.)
• Consequence: DNAH14 NM_001367479.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.81
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-225367810-C-T is Benign according to our data. Variant chr1-225367810-C-T is described in ClinVar as Benign. ClinVar VariationId is 402661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.12096C>T	p.Ala4032Ala	synonymous_variant	Exon 77 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.12096C>T	p.Ala4032Ala	synonymous_variant	Exon 77 of 86		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67664 AN: 151892 Hom.: 16715 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.458 AC: 70169 AN: 153326 AF XY: 0.456

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.522 AC: 727489 AN: 1393522 Hom.: 196709 Cov.: 32 AF XY: 0.518 AC XY: 356017 AN XY: 687536

African (AFR) AF: 0.237 AC: 7469 AN: 31482

American (AMR) AF: 0.399 AC: 14206 AN: 35608

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 16050 AN: 25102

East Asian (EAS) AF: 0.211 AC: 7531 AN: 35708

South Asian (SAS) AF: 0.319 AC: 25168 AN: 79020

European-Finnish (FIN) AF: 0.565 AC: 27799 AN: 49192

Middle Eastern (MID) AF: 0.622 AC: 3539 AN: 5690

European-Non Finnish (NFE) AF: 0.555 AC: 596225 AN: 1073940

Other (OTH) AF: 0.511 AC: 29502 AN: 57780

GnomAD4 genome AF: 0.445 AC: 67673 AN: 152010 Hom.: 16717 Cov.: 32 AF XY: 0.442 AC XY: 32804 AN XY: 74300

African (AFR) AF: 0.246 AC: 10200 AN: 41460

American (AMR) AF: 0.463 AC: 7068 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1120 AN: 5170

South Asian (SAS) AF: 0.293 AC: 1408 AN: 4812

European-Finnish (FIN) AF: 0.565 AC: 5961 AN: 10546

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38037 AN: 67952

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.526 Hom.: 12615

Bravo AF: 0.430

Asia WGS AF: 0.273 AC: 950 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	-0.57
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-1.8
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: rs11578981; hg19: chr1-225555512; COSMIC: COSV59897920;