1-225252286-T-C

Variant names:

• chr1-225252286-T-C
• rs630120
• NM_001367479.1:c.6749-15T>C

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.6749-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,401,128 control chromosomes in the GnomAD database, including 61,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12787 hom., cov: 32)
  • Exomes 𝑓: 0.26 (48683 hom.)
• Consequence: DNAH14 NM_001367479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.566
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-225252286-T-C is Benign according to our data. Variant chr1-225252286-T-C is described in ClinVar as Benign. ClinVar VariationId is 402652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.6749-15T>C		intron_variant	Intron 43 of 85	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.6749-15T>C		intron_variant	Intron 43 of 85		NM_001367479.1	ENSP00000508305.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55572 AN: 151888 Hom.: 12750 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.324 AC: 50385 AN: 155532 AF XY: 0.316

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.623

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.260 AC: 324192 AN: 1249124 Hom.: 48683 Cov.: 18 AF XY: 0.260 AC XY: 162457 AN XY: 624182

African (AFR) AF: 0.634 AC: 18197 AN: 28686

American (AMR) AF: 0.444 AC: 15659 AN: 35268

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 5817 AN: 24220

East Asian (EAS) AF: 0.586 AC: 20389 AN: 34786

South Asian (SAS) AF: 0.349 AC: 26408 AN: 75642

European-Finnish (FIN) AF: 0.200 AC: 9836 AN: 49098

Middle Eastern (MID) AF: 0.238 AC: 1283 AN: 5400

European-Non Finnish (NFE) AF: 0.224 AC: 211125 AN: 943016

Other (OTH) AF: 0.292 AC: 15478 AN: 53008

GnomAD4 genome AF: 0.366 AC: 55667 AN: 152004 Hom.: 12787 Cov.: 32 AF XY: 0.366 AC XY: 27222 AN XY: 74302

African (AFR) AF: 0.618 AC: 25605 AN: 41446

American (AMR) AF: 0.394 AC: 6013 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3468

East Asian (EAS) AF: 0.607 AC: 3125 AN: 5152

South Asian (SAS) AF: 0.381 AC: 1840 AN: 4826

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10588

Middle Eastern (MID) AF: 0.252 AC: 73 AN: 290

European-Non Finnish (NFE) AF: 0.223 AC: 15176 AN: 67940

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.285 Hom.: 1682

Bravo AF: 0.395

Asia WGS AF: 0.508 AC: 1766 AN: 3474

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	-0.92
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs630120; hg19: chr1-225439988; COSMIC: COSV59895696;