rs560792252

Variant names:

• chr1-225272064-T-C
• rs560792252
• NM_001367479.1:c.7830T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-225272064-T-C
• chr1-225272064-T-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001367479.1(DNAH14):​c.7830T>C​(p.Asp2610Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000876 in 1,549,486 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: DNAH14 NM_001367479.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-225272064-T-C is Benign according to our data. Variant chr1-225272064-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 402667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.

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.7830T>C	p.Asp2610Asp	synonymous	Exon 51 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.7830T>C	p.Asp2610Asp	synonymous	Exon 51 of 86	ENSP00000508305.1	A0A804HLD3
	DNAH14	ENST00000327794.10	TSL:1	n.952-891T>C		intron	N/A	ENSP00000328980.6	H7BXS7
	DNAH14	ENST00000430092.5	TSL:5	c.7812T>C	p.Asp2604Asp	synonymous	Exon 51 of 84	ENSP00000414402.1	Q0VDD8-4

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000754 AC: 115 AN: 152472 AF XY: 0.000803

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000536

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000132

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.000465

GnomAD4 exome AF: 0.000913 AC: 1275 AN: 1397180 Hom.: 1 Cov.: 30 AF XY: 0.000929 AC XY: 640 AN XY: 689122

African (AFR) AF: 0.0000317 AC: 1 AN: 31520

American (AMR) AF: 0.000424 AC: 15 AN: 35358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35592

South Asian (SAS) AF: 0.000925 AC: 73 AN: 78890

European-Finnish (FIN) AF: 0.000143 AC: 7 AN: 49060

Middle Eastern (MID) AF: 0.00451 AC: 25 AN: 5548

European-Non Finnish (NFE) AF: 0.00102 AC: 1096 AN: 1078180

Other (OTH) AF: 0.00100 AC: 58 AN: 57896

GnomAD4 genome AF: 0.000545 AC: 83 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74486

African (AFR) AF: 0.0000722 AC: 3 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000748 Hom.: 0

Bravo AF: 0.000597

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.3
DANN	Benign	0.52
PhyloP100		1.0
Mutation Taster		=99/1	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: rs560792252; hg19: chr1-225459766;