rs7926700

chr11-103324076-C-Gchr11-103324076-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080463.2(DYNC2H1):c.12060+86C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 697,124 control chromosomes in the GnomAD database, including 933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (639 hom., cov: 32)
  • Exomes 𝑓: 0.020 (294 hom.)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-103324076-C-G is Benign according to our data. Variant chr11-103324076-C-G is described in ClinVar as [Benign]. Clinvar id is 675083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2	c.12060+86C>G		intron_variant		ENST00000650373.2
DYNC2H1	NM_001377.3	c.12039+86C>G		intron_variant		ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000375735.7	c.12039+86C>G		intron_variant		1	NM_001377.3	P3
DYNC2H1	ENST00000650373.2	c.12060+86C>G		intron_variant			NM_001080463.2	A1
DYNC2H1	ENST00000334267.11	c.2206-111867C>G		intron_variant		1
DYNC2H1	ENST00000528670.5	c.*85+86C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8860 AN: 152070 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0490

GnomAD4 exome AF: 0.0201 AC: 10938 AN: 544936 Hom.: 294 AF XY: 0.0199 AC XY: 5477 AN XY: 274596

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0555

Gnomad4 EAS exome AF: 0.0000383

Gnomad4 SAS exome AF: 0.00524

Gnomad4 FIN exome AF: 0.00655

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0315

GnomAD4 genome AF: 0.0583 AC: 8876 AN: 152188 Hom.: 639 Cov.: 32 AF XY: 0.0567 AC XY: 4223 AN XY: 74424

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0583

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0475

Alfa AF: 0.00941 Hom.: 9

Bravo AF: 0.0650

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.19
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs7926700; hg19: chr11-103194804;