rs786205668

Variant names:

• chr1-225100772-T-A
• rs786205668
• NM_001367479.1:c.3755T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 6P and 2B. PM2 PP3_Strong BP6_Moderate

The NM_001367479.1(DNAH14):​c.3755T>A​(p.Met1252Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH14 NM_001367479.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944
• BP6: Variant 1-225100772-T-A is Benign according to our data. Variant chr1-225100772-T-A is described in ClinVar as Benign. ClinVar VariationId is 190455.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.3755T>A	p.Met1252Lys	missense_variant	Exon 23 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1	c.3755T>A	p.Met1252Lys	missense_variant	Exon 23 of 86		NM_001367479.1	ENSP00000508305.1
DNAH14	ENST00000430092.5	c.3755T>A	p.Met1252Lys	missense_variant	Exon 23 of 84	5		ENSP00000414402.1
DNAH14	ENST00000439375.6	c.3755T>A	p.Met1252Lys	missense_variant	Exon 22 of 83	5		ENSP00000392061.2
DNAH14	ENST00000445597.6	c.3051+14983T>A		intron_variant	Intron 16 of 60	5		ENSP00000409472.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-immune hydrops fetalis Benign:1

-

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	0.14
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.43	T;.
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.31	T
PhyloP100		0.81
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.56	P;P
Vest4		0.72
MutPred		0.82		Loss of stability (P = 0.0188);Loss of stability (P = 0.0188);
MVP		0.58
ClinPred		0.62	D
GERP RS		1.8
Mutation Taster		=94/6	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: rs786205668; hg19: chr1-225288474;