rs3128652

Variant names:

• chr1-225080644-G-A
• rs3128652
• NM_001367479.1:c.3032G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-225080644-G-A
• chr1-225080644-G-C
• chr1-225080644-G-T

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.3032G>A​(p.Arg1011Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,551,374 control chromosomes in the GnomAD database, including 663,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (51621 hom., cov: 33)
  • Exomes 𝑓: 0.93 (612314 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.59
• Publications: 20 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
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.8557279E-6).
• BP6: Variant 1-225080644-G-A is Benign according to our data. Variant chr1-225080644-G-A is described in ClinVar as Benign. ClinVar VariationId is 402648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.3032G>A	p.Arg1011Gln	missense	Exon 19 of 86	NP_001354408.1	A0A804HLD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.3032G>A	p.Arg1011Gln	missense	Exon 19 of 86	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000430092.5	TSL:5	c.3032G>A	p.Arg1011Gln	missense	Exon 19 of 84	ENSP00000414402.1	Q0VDD8-4
	DNAH14	ENST00000439375.6	TSL:5	c.3032G>A	p.Arg1011Gln	missense	Exon 18 of 83	ENSP00000392061.2	Q0VDD8-4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121013 AN: 151750 Hom.: 51603 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.824

GnomAD2 exomes AF: 0.869 AC: 137287 AN: 157894 AF XY: 0.879

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.927

Gnomad EAS exome AF: 0.702

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.891

GnomAD4 exome AF: 0.931 AC: 1302663 AN: 1399506 Hom.: 612314 Cov.: 55 AF XY: 0.931 AC XY: 642618 AN XY: 690238

African (AFR) AF: 0.455 AC: 14358 AN: 31564

American (AMR) AF: 0.766 AC: 27334 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 23299 AN: 25168

East Asian (EAS) AF: 0.738 AC: 26359 AN: 35718

South Asian (SAS) AF: 0.869 AC: 68808 AN: 79182

European-Finnish (FIN) AF: 0.968 AC: 47912 AN: 49472

Middle Eastern (MID) AF: 0.915 AC: 5215 AN: 5698

European-Non Finnish (NFE) AF: 0.962 AC: 1037411 AN: 1078928

Other (OTH) AF: 0.894 AC: 51967 AN: 58098

GnomAD4 genome AF: 0.797 AC: 121067 AN: 151868 Hom.: 51621 Cov.: 33 AF XY: 0.797 AC XY: 59174 AN XY: 74228

African (AFR) AF: 0.472 AC: 19519 AN: 41366

American (AMR) AF: 0.796 AC: 12146 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3176 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3681 AN: 5144

South Asian (SAS) AF: 0.852 AC: 4089 AN: 4802

European-Finnish (FIN) AF: 0.967 AC: 10245 AN: 10590

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

European-Non Finnish (NFE) AF: 0.962 AC: 65330 AN: 67918

Other (OTH) AF: 0.824 AC: 1737 AN: 2108

Alfa AF: 0.902 Hom.: 127687

Bravo AF: 0.769

TwinsUK AF: 0.960 AC: 3560

ALSPAC AF: 0.955 AC: 3679

ESP6500AA AF: 0.519 AC: 718

ESP6500EA AF: 0.961 AC: 3057

ExAC AF: 0.859 AC: 21026

Asia WGS AF: 0.753 AC: 2622 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.012
DANN	Benign	0.71
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.6
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.0060
Sift	Benign	1.0	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.073
ClinPred		0.00069	T
GERP RS		-6.7
Varity_R		0.018
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: rs3128652; hg19: chr1-225268346; COSMIC: COSV60741191;