rs1798531

Variant names:

• chr16-70921012-G-T
• rs1798531
• NM_001270974.2:c.7364C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-70921012-G-T
• chr16-70921012-G-A
• chr16-70921012-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001270974.2(HYDIN):​c.7364C>A​(p.Pro2455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 151,308 control chromosomes in the GnomAD database, including 75,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75286 hom., cov: 24)
  • Exomes 𝑓: 1.0 (707428 hom.)
  • Failed GnomAD Quality Control
• Consequence: HYDIN NM_001270974.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.45
• Publications: 26 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.8863645E-7).
• BP6: Variant 16-70921012-G-T is Benign according to our data. Variant chr16-70921012-G-T is described in ClinVar as Benign. ClinVar VariationId is 402954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

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.7364C>A	p.Pro2455Gln	missense	Exon 46 of 86	NP_001257903.1	Q4G0P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYDIN	ENST00000393567.7	TSL:5 MANE Select	c.7364C>A	p.Pro2455Gln	missense	Exon 46 of 86	ENSP00000377197.2	Q4G0P3-1
	HYDIN	ENST00000309900.11	TSL:1	n.2036C>A		non_coding_transcript_exon	Exon 12 of 20

Frequencies

GnomAD3 genomes AF: 0.998 AC: 150821 AN: 151190 Hom.: 75227 Cov.: 24

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.998

GnomAD2 exomes AF: 0.997 AC: 199260 AN: 199800 AF XY: 0.997

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.995

Gnomad OTH exome AF: 0.996

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.997 AC: 1418969 AN: 1423256 Hom.: 707428 Cov.: 25 AF XY: 0.997 AC XY: 705764 AN XY: 707820

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 1.00 AC: 32078 AN: 32094

American (AMR) AF: 0.999 AC: 40269 AN: 40310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 24446 AN: 24452

East Asian (EAS) AF: 1.00 AC: 39542 AN: 39542

South Asian (SAS) AF: 0.999 AC: 81175 AN: 81268

European-Finnish (FIN) AF: 0.999 AC: 52012 AN: 52082

Middle Eastern (MID) AF: 1.00 AC: 5570 AN: 5572

European-Non Finnish (NFE) AF: 0.996 AC: 1085178 AN: 1089112

Other (OTH) AF: 0.998 AC: 58699 AN: 58824

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.998 AC: 150939 AN: 151308 Hom.: 75286 Cov.: 24 AF XY: 0.998 AC XY: 73672 AN XY: 73830

African (AFR) AF: 0.999 AC: 41133 AN: 41170

American (AMR) AF: 0.998 AC: 15167 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5140 AN: 5140

South Asian (SAS) AF: 0.999 AC: 4694 AN: 4698

European-Finnish (FIN) AF: 0.999 AC: 10502 AN: 10512

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67556 AN: 67832

Other (OTH) AF: 0.998 AC: 2075 AN: 2080

Alfa AF: 0.996 Hom.: 106391

Bravo AF: 0.997

ESP6500AA AF: 0.999 AC: 3580

ESP6500EA AF: 0.991 AC: 7999

ExAC AF: 0.993 AC: 119175

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.24
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.064	N
MetaRNN	Benign	5.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N
PhyloP100		2.4
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Vest4		0.038
ClinPred		0.011	T
GERP RS		5.9
Varity_R		0.024
gMVP		0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1798531; hg19: chr16-70954915; COSMIC: COSV107376356;