rs191012679

chr11-103187355-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001080463.2(DYNC2H1):c.6909C>T(p.Tyr2303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,612,860 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: DYNC2H1 NM_001080463.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.622

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 11-103187355-C-T is Benign according to our data. Variant chr11-103187355-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.622 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2H1	NM_001080463.2	c.6909C>T	p.Tyr2303=	synonymous_variant	43/90	ENST00000650373.2
DYNC2H1	NM_001377.3	c.6909C>T	p.Tyr2303=	synonymous_variant	43/89	ENST00000375735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2H1	ENST00000650373.2	c.6909C>T	p.Tyr2303=	synonymous_variant	43/90		NM_001080463.2	A1
DYNC2H1	ENST00000375735.7	c.6909C>T	p.Tyr2303=	synonymous_variant	43/89	1	NM_001377.3	P3
DYNC2H1	ENST00000334267.11	c.2205+52936C>T		intron_variant		1
DYNC2H1	ENST00000649323.1	c.*4454C>T		3_prime_UTR_variant, NMD_transcript_variant	41/51

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 293 AN: 151988 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000564 AC: 140 AN: 248382 Hom.: 0 AF XY: 0.000408 AC XY: 55 AN XY: 134732

Gnomad AFR exome AF: 0.00614

Gnomad AMR exome AF: 0.000756

Gnomad ASJ exome AF: 0.000697

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000263 AC: 384 AN: 1460754 Hom.: 2 Cov.: 30 AF XY: 0.000231 AC XY: 168 AN XY: 726660

Gnomad4 AFR exome AF: 0.00664

Gnomad4 AMR exome AF: 0.000717

Gnomad4 ASJ exome AF: 0.000728

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.000647

GnomAD4 genome AF: 0.00193 AC: 294 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.00192 AC XY: 143 AN XY: 74352

Gnomad4 AFR AF: 0.00631

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00226

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 11, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2019

- -

Jeune thoracic dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	4.8
Dann	Benign	0.32

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

LitVar

Other links and lift over

dbSNP: rs191012679; hg19: chr11-103058084; COSMIC: COSV62100950;