NM_001270974.2:c.922A>T

Variant names:

• chr16-71137272-T-A
• rs397515414
• NM_001270974.2:c.922A>T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001270974.2(HYDIN):​c.922A>T​(p.Lys308*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HYDIN NM_001270974.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.70
• Publications: 3 publications found

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]

HYDIN Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-71137272-T-A is Pathogenic according to our data. Variant chr16-71137272-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 39699.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270974.2. 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
	HYDIN	NM_001270974.2	MANE Select	c.922A>T	p.Lys308*	stop_gained	Exon 8 of 86	NP_001257903.1	Q4G0P3-1
	HYDIN	NM_017558.5		c.922A>T	p.Lys308*	stop_gained	Exon 8 of 20	NP_060028.2
	HYDIN	NM_001198542.1		c.1003A>T	p.Lys335*	stop_gained	Exon 8 of 19	NP_001185471.1	Q4G0P3-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.922A>T	p.Lys308*	stop_gained	Exon 8 of 86	ENSP00000377197.2	Q4G0P3-1
	HYDIN	ENST00000288168.14	TSL:1	c.973A>T	p.Lys325*	stop_gained	Exon 8 of 15	ENSP00000288168.10	F8WD03
	HYDIN	ENST00000539447.5	TSL:1	n.*170A>T		non_coding_transcript_exon	Exon 6 of 19	ENSP00000463093.1	J3KTP9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000185 AC: 1 AN: 539810 Hom.: 0 Cov.: 6 AF XY: 0.00000348 AC XY: 1 AN XY: 287208

African (AFR) AF: 0.00 AC: 0 AN: 14660

American (AMR) AF: 0.00 AC: 0 AN: 28060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16606

East Asian (EAS) AF: 0.00 AC: 0 AN: 32568

South Asian (SAS) AF: 0.00 AC: 0 AN: 52946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2370

European-Non Finnish (NFE) AF: 0.00000304 AC: 1 AN: 329190

Other (OTH) AF: 0.00 AC: 0 AN: 29488

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Primary ciliary dyskinesia 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=1/199	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs397515414; hg19: chr16-71171175;