16-70807898-GGGGATGATATA-TATATCATC

Position:

• chr16-70807898-GGGGATGATATA-TATATCATC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4_Supporting PP3 PP5_Moderate

The NM_001270974.2(HYDIN):​c.15037_15048delinsGATGATATA​(p.Tyr5013_Pro5016delinsAspAspIle) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HYDIN NM_001270974.2 protein_altering
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.95

Genes affected

HYDIN (HGNC:19368): (HYDIN axonemal central pair apparatus protein) This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001270974.2. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 16-70807898-GGGGATGATATA-TATATCATC is Pathogenic according to our data. Variant chr16-70807898-GGGGATGATATA-TATATCATC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3027471.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYDIN	NM_001270974.2	c.15037_15048delinsGATGATATA	p.Tyr5013_Pro5016delinsAspAspIle	protein_altering_variant	86/86	ENST00000393567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7	c.15037_15048delinsGATGATATA	p.Tyr5013_Pro5016delinsAspAspIle	protein_altering_variant	86/86	5	NM_001270974.2	P1
HYDIN	ENST00000378856.8	c.*3917_*3928delinsGATGATATA		3_prime_UTR_variant, NMD_transcript_variant	22/22	1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 5 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Royal Brompton Clinical Genetics And Genomics Laboratory, NHS South East Genomic Laboratory Hub

Mar 06, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-70841801;