11-103109638-G-C

Variant summary

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

The NM_001080463.2(DYNC2H1):c.64G>C(p.Gly22Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G22G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DYNC2H1 NM_001080463.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.41

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-103109638-G-C is Benign according to our data. Variant chr11-103109638-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 698370.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2	c.64G>C	p.Gly22Arg	missense_variant	1/90	ENST00000650373.2
DYNC2H1	NM_001377.3	c.64G>C	p.Gly22Arg	missense_variant	1/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.64G>C	p.Gly22Arg	missense_variant	1/90		NM_001080463.2	A1
DYNC2H1	ENST00000375735.7	c.64G>C	p.Gly22Arg	missense_variant	1/89	1	NM_001377.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000281 AC: 7 AN: 249114 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

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: 0.00

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Uncertain	0.10
Cadd	Uncertain	25
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;.;D;D;.;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
Polyphen		0.99, 1.0, 1.0	.;D;D;D;D;D
Vest4		0.76, 0.87, 0.78
MutPred		0.58		Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);
MVP		0.60
MPC		0.17
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.69
gMVP		0.74

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: rs751464413; hg19: chr11-102980367;