1-224964551-C-T

Variant names:

• chr1-224964551-C-T
• rs41267349
• NM_001367479.1:c.440C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001367479.1(DNAH14):​c.440C>T​(p.Pro147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,608,164 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (63 hom.)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.607
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048256814).
• BP6: Variant 1-224964551-C-T is Benign according to our data. Variant chr1-224964551-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.440C>T	p.Pro147Leu	missense	Exon 5 of 86	NP_001354408.1	A0A804HLD3
	DNAH14	NM_001145154.3		c.440C>T	p.Pro147Leu	missense	Exon 5 of 11	NP_001138626.1	Q0VDD8-2
	DNAH14	NM_001349911.2		c.440C>T	p.Pro147Leu	missense	Exon 5 of 11	NP_001336840.1	M9MMK7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	ENST00000682510.1	MANE Select	c.440C>T	p.Pro147Leu	missense	Exon 5 of 86	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000400952.7	TSL:1	c.440C>T	p.Pro147Leu	missense	Exon 5 of 11	ENSP00000383737.3	Q0VDD8-2
	DNAH14	ENST00000366849.5	TSL:1	c.440C>T	p.Pro147Leu	missense	Exon 5 of 11	ENSP00000355814.1	M9MMK7

Frequencies

GnomAD3 genomes AF: 0.00629 AC: 956 AN: 151940 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00392

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00331

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00887

Gnomad OTH AF: 0.00768

GnomAD2 exomes AF: 0.00584 AC: 1454 AN: 248858 AF XY: 0.00588

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.00329

Gnomad ASJ exome AF: 0.00785

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00311

Gnomad NFE exome AF: 0.00907

Gnomad OTH exome AF: 0.00546

GnomAD4 exome AF: 0.00773 AC: 11261 AN: 1456106 Hom.: 63 Cov.: 30 AF XY: 0.00750 AC XY: 5430 AN XY: 724238

African (AFR) AF: 0.00240 AC: 80 AN: 33386

American (AMR) AF: 0.00363 AC: 162 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 240 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00255 AC: 217 AN: 85058

European-Finnish (FIN) AF: 0.00416 AC: 221 AN: 53182

Middle Eastern (MID) AF: 0.00419 AC: 24 AN: 5726

European-Non Finnish (NFE) AF: 0.00890 AC: 9863 AN: 1108634

Other (OTH) AF: 0.00756 AC: 454 AN: 60072

GnomAD4 genome AF: 0.00629 AC: 957 AN: 152058 Hom.: 5 Cov.: 32 AF XY: 0.00599 AC XY: 445 AN XY: 74302

African (AFR) AF: 0.00390 AC: 162 AN: 41500

American (AMR) AF: 0.00439 AC: 67 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00331 AC: 35 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00889 AC: 604 AN: 67964

Other (OTH) AF: 0.00760 AC: 16 AN: 2106

Alfa AF: 0.00766 Hom.: 22

Bravo AF: 0.00589

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00363 AC: 13

ESP6500EA AF: 0.00652 AC: 53

ExAC AF: 0.00591 AC: 714

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.050
Sift	Benign	0.19	T
Sift4G	Uncertain	0.013	D
Polyphen		0.013	B
Vest4		0.15
MVP		0.38
MPC		0.056
ClinPred		0.010	T
GERP RS		0.60
Varity_R		0.059
gMVP		0.23
Mutation Taster		=100/0	polymorphism

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: rs41267349; hg19: chr1-225152253;