1-225377371-C-T

Variant names:

• chr1-225377371-C-T
• rs3856155
• NM_001367479.1:c.12651C>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.12651C>T​(p.Gly4217Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,549,410 control chromosomes in the GnomAD database, including 267,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (22033 hom., cov: 31)
  • Exomes 𝑓: 0.59 (245035 hom.)
• Consequence: DNAH14 NM_001367479.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.636
• Publications: 13 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=-0.66).
• BP6: Variant 1-225377371-C-T is Benign according to our data. Variant chr1-225377371-C-T is described in ClinVar as Benign. ClinVar VariationId is 402665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.636 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.12651C>T	p.Gly4217Gly	synonymous_variant	Exon 79 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.12651C>T	p.Gly4217Gly	synonymous_variant	Exon 79 of 86		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77373 AN: 151888 Hom.: 22032 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.558

GnomAD2 exomes AF: 0.584 AC: 89204 AN: 152646 AF XY: 0.572

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.714

Gnomad ASJ exome AF: 0.663

Gnomad EAS exome AF: 0.743

Gnomad FIN exome AF: 0.603

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.620

GnomAD4 exome AF: 0.586 AC: 818789 AN: 1397404 Hom.: 245035 Cov.: 50 AF XY: 0.581 AC XY: 400591 AN XY: 689168

African (AFR) AF: 0.216 AC: 6798 AN: 31542

American (AMR) AF: 0.710 AC: 25204 AN: 35484

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 16658 AN: 25132

East Asian (EAS) AF: 0.751 AC: 26783 AN: 35682

South Asian (SAS) AF: 0.407 AC: 32078 AN: 78846

European-Finnish (FIN) AF: 0.607 AC: 29868 AN: 49238

Middle Eastern (MID) AF: 0.637 AC: 3628 AN: 5692

European-Non Finnish (NFE) AF: 0.597 AC: 643905 AN: 1077872

Other (OTH) AF: 0.585 AC: 33867 AN: 57916

GnomAD4 genome AF: 0.509 AC: 77386 AN: 152006 Hom.: 22033 Cov.: 31 AF XY: 0.512 AC XY: 38006 AN XY: 74302

African (AFR) AF: 0.236 AC: 9782 AN: 41440

American (AMR) AF: 0.679 AC: 10376 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2296 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3851 AN: 5186

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4812

European-Finnish (FIN) AF: 0.605 AC: 6393 AN: 10560

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40934 AN: 67946

Other (OTH) AF: 0.557 AC: 1175 AN: 2110

Alfa AF: 0.546 Hom.: 11599

Bravo AF: 0.510

Asia WGS AF: 0.525 AC: 1828 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	-0.66
CADD	Benign	2.2
DANN	Benign	0.23
PhyloP100		-0.64
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: rs3856155; hg19: chr1-225565073; COSMIC: COSV59897933;