chr1-225042906-C-T

Variant names:

• chr1-225042906-C-T
• rs2501107
• NM_001367479.1:c.1560C>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.1560C>T​(p.Cys520Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,551,486 control chromosomes in the GnomAD database, including 663,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (51686 hom., cov: 31)
  • Exomes 𝑓: 0.93 (611735 hom.)
• Consequence: DNAH14 NM_001367479.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.314
• 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=-0.74).
• BP6: Variant 1-225042906-C-T is Benign according to our data. Variant chr1-225042906-C-T is described in ClinVar as Benign. ClinVar VariationId is 402644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.314 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.1560C>T	p.Cys520Cys	synonymous_variant	Exon 13 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.1560C>T	p.Cys520Cys	synonymous_variant	Exon 13 of 86		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.1560C>T	p.Cys520Cys	synonymous_variant	Exon 13 of 84	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.1560C>T	p.Cys520Cys	synonymous_variant	Exon 12 of 83	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.1617C>T	p.Cys539Cys	synonymous_variant	Exon 11 of 61	5		ENSP00000409472.2

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121134 AN: 152008 Hom.: 51668 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.823

GnomAD2 exomes AF: 0.869 AC: 136548 AN: 157066 AF XY: 0.879

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.927

Gnomad EAS exome AF: 0.702

Gnomad FIN exome AF: 0.969

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.889

GnomAD4 exome AF: 0.930 AC: 1301811 AN: 1399360 Hom.: 611735 Cov.: 50 AF XY: 0.931 AC XY: 642256 AN XY: 690180

African (AFR) AF: 0.451 AC: 14252 AN: 31598

American (AMR) AF: 0.766 AC: 27342 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 23302 AN: 25176

East Asian (EAS) AF: 0.724 AC: 25862 AN: 35710

South Asian (SAS) AF: 0.869 AC: 68820 AN: 79228

European-Finnish (FIN) AF: 0.968 AC: 47736 AN: 49294

Middle Eastern (MID) AF: 0.915 AC: 5216 AN: 5698

European-Non Finnish (NFE) AF: 0.962 AC: 1037418 AN: 1078942

Other (OTH) AF: 0.894 AC: 51863 AN: 58010

GnomAD4 genome AF: 0.797 AC: 121186 AN: 152126 Hom.: 51686 Cov.: 31 AF XY: 0.796 AC XY: 59240 AN XY: 74380

African (AFR) AF: 0.470 AC: 19461 AN: 41430

American (AMR) AF: 0.796 AC: 12166 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3182 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3674 AN: 5172

South Asian (SAS) AF: 0.852 AC: 4107 AN: 4820

European-Finnish (FIN) AF: 0.968 AC: 10270 AN: 10614

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65447 AN: 68024

Other (OTH) AF: 0.823 AC: 1735 AN: 2108

Alfa AF: 0.892 Hom.: 47806

Bravo AF: 0.768

Asia WGS AF: 0.752 AC: 2618 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	-0.74
CADD	Benign	7.9
DANN	Benign	0.51
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2501107; hg19: chr1-225230608; COSMIC: COSV108255844;