chr1-225290091-T-G

Variant names:

• chr1-225290091-T-G
• rs12042900
• NM_001367479.1:c.8469+9T>G

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.8469+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,393,896 control chromosomes in the GnomAD database, including 91,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8135 hom., cov: 32)
  • Exomes 𝑓: 0.36 (83707 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0570
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-225290091-T-G is Benign according to our data. Variant chr1-225290091-T-G is described in ClinVar as [Benign]. Clinvar id is 402654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.8469+9T>G		intron_variant	Intron 55 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.8469+9T>G		intron_variant	Intron 55 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47144 AN: 151912 Hom.: 8129 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.312

GnomAD2 exomes AF: 0.389 AC: 34697 AN: 89272 AF XY: 0.393

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.363 AC: 450356 AN: 1241866 Hom.: 83707 Cov.: 31 AF XY: 0.365 AC XY: 219459 AN XY: 601964

African (AFR) AF: 0.143 AC: 3856 AN: 26978

American (AMR) AF: 0.418 AC: 7722 AN: 18470

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 6644 AN: 19604

East Asian (EAS) AF: 0.476 AC: 15339 AN: 32214

South Asian (SAS) AF: 0.443 AC: 23374 AN: 52822

European-Finnish (FIN) AF: 0.392 AC: 17298 AN: 44102

Middle Eastern (MID) AF: 0.264 AC: 1090 AN: 4136

European-Non Finnish (NFE) AF: 0.360 AC: 357527 AN: 993278

Other (OTH) AF: 0.348 AC: 17506 AN: 50262

GnomAD4 genome AF: 0.310 AC: 47163 AN: 152030 Hom.: 8135 Cov.: 32 AF XY: 0.314 AC XY: 23362 AN XY: 74316

African (AFR) AF: 0.156 AC: 6470 AN: 41540

American (AMR) AF: 0.378 AC: 5767 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2289 AN: 5156

South Asian (SAS) AF: 0.440 AC: 2122 AN: 4826

European-Finnish (FIN) AF: 0.373 AC: 3941 AN: 10558

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

European-Non Finnish (NFE) AF: 0.359 AC: 24352 AN: 67892

Other (OTH) AF: 0.314 AC: 662 AN: 2108

Alfa AF: 0.323 Hom.: 3195

Bravo AF: 0.303

Asia WGS AF: 0.451 AC: 1567 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	-0.69
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12042900; hg19: chr1-225477793; COSMIC: COSV59897055;