11-103152201-T-G

Position:

• chr11-103152201-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001377.3(DYNC2H1):​c.3012T>G​(p.Gly1004Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYNC2H1 NM_001377.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.356 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2H1	NM_001080463.2	c.3012T>G	p.Gly1004Gly	synonymous_variant	21/90	ENST00000650373.2	NP_001073932.1
DYNC2H1	NM_001377.3	c.3012T>G	p.Gly1004Gly	synonymous_variant	21/89	ENST00000375735.7	NP_001368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.3012T>G	p.Gly1004Gly	synonymous_variant	21/90		NM_001080463.2	ENSP00000497174.1
DYNC2H1	ENST00000375735.7	c.3012T>G	p.Gly1004Gly	synonymous_variant	21/89	1	NM_001377.3	ENSP00000364887.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00221 AC: 533 AN: 241642 Hom.: 0 AF XY: 0.00209 AC XY: 274 AN XY: 131288

Gnomad AFR exome AF: 0.00303

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00202

Gnomad SAS exome AF: 0.000407

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.000849

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000239 AC: 347 AN: 1454446 Hom.: 0 Cov.: 33 AF XY: 0.000246 AC XY: 178 AN XY: 723076

Gnomad4 AFR exome AF: 0.000692

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00203

Gnomad4 SAS exome AF: 0.0000709

Gnomad4 FIN exome AF: 0.000723

Gnomad4 NFE exome AF: 0.0000721

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome Cov.: 31

EpiCase AF: 0.00

EpiControl AF: 0.000542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.7
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs202082545; hg19: chr11-103022930;