rs786205668

Positions:

• chr1-225100772-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 10/15 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 190455.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-225100772-T-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1	c.3755T>A	p.Met1252Lys	missense_variant	23/86	ENST00000682510.1	NP_001354408.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-immune hydrops fetalis Benign:1

Benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs786205668; hg19: chr1-225288474;