rs201302396

chr11-103170227-G-Achr11-103170227-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001080463.2(DYNC2H1):c.5088G>A(p.Thr1696=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,612,080 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: DYNC2H1 NM_001080463.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

Genes affected

DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-103170227-G-A is Benign according to our data. Variant chr11-103170227-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2	c.5088G>A	p.Thr1696=	synonymous_variant	33/90	ENST00000650373.2
DYNC2H1	NM_001377.3	c.5088G>A	p.Thr1696=	synonymous_variant	33/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.5088G>A	p.Thr1696=	synonymous_variant	33/90		NM_001080463.2	A1
DYNC2H1	ENST00000375735.7	c.5088G>A	p.Thr1696=	synonymous_variant	33/89	1	NM_001377.3	P3
DYNC2H1	ENST00000334267.11	c.2205+35808G>A		intron_variant		1
DYNC2H1	ENST00000649323.1	c.*2633G>A		3_prime_UTR_variant, NMD_transcript_variant	31/51

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152144 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000142 AC: 35 AN: 246342 Hom.: 0 AF XY: 0.000135 AC XY: 18 AN XY: 133614

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000563

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1459818 Hom.: 1 Cov.: 30 AF XY: 0.000113 AC XY: 82 AN XY: 726076

Gnomad4 AFR exome AF: 0.00341

Gnomad4 AMR exome AF: 0.0000449

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000557

Gnomad4 SAS exome AF: 0.0000466

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152262 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74434

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.000880

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Jeune thoracic dystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	3.8
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs201302396; hg19: chr11-103040956;