11-103117775-A-G

Variant names:

• chr11-103117775-A-G
• NM_001080463.2:c.911A>G

Variant summary

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

The NM_001377.3(DYNC2H1):​c.911A>G​(p.Gln304Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q304L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DYNC2H1 NM_001377.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.88

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.911A>G	p.Gln304Arg	missense_variant	Exon 6 of 90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.911A>G	p.Gln304Arg	missense_variant	Exon 6 of 89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.911A>G	p.Gln304Arg	missense_variant	Exon 6 of 90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.911A>G	p.Gln304Arg	missense_variant	Exon 6 of 89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461190 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T;.;T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;.;D;T;.;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.9	.;M;M;M;M;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	.;N;N;.;.;N
REVEL	Uncertain	0.34
Sift	Benign	0.21	.;T;T;.;.;T
Sift4G	Benign	0.49	.;T;T;.;.;T
Polyphen		0.34, 1.0, 0.18	.;B;D;B;B;B
Vest4		0.69, 0.84, 0.69
MutPred		0.53		Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);Gain of MoRF binding (P = 0.0104);
MVP		0.73
MPC		0.11
ClinPred		0.85	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-102988504;