16-70808065-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001270974.2(HYDIN):c.14884-4_14884-3insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,444,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: HYDIN NM_001270974.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-70808065-G-GA is Benign according to our data. Variant chr16-70808065-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 2646688.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.14884-4_14884-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000393567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYDIN	ENST00000393567.7	c.14884-4_14884-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001270974.2	P1
HYDIN	ENST00000378856.8	c.*3764-4_*3764-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000127 AC: 3 AN: 236264 Hom.: 0 AF XY: 0.0000157 AC XY: 2 AN XY: 127600

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000554 AC: 8 AN: 1444682 Hom.: 0 Cov.: 31 AF XY: 0.00000419 AC XY: 3 AN XY: 716494

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000726

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

HYDIN: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1267124382; hg19: chr16-70841968;