NM_001080463.2:c.10482+96T>C

Variant names:

• chr11-103256336-T-C
• rs12294076
• NM_001080463.2:c.10482+96T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080463.2(DYNC2H1):​c.10482+96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,250,336 control chromosomes in the GnomAD database, including 1,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (1058 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (701 hom.)
• Consequence: DYNC2H1 NM_001080463.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0120
• Publications: 4 publications found

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]

DYNC2H1 Gene-Disease associations (from GenCC):

• asphyxiating thoracic dystrophy 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Verma-Naumoff type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285878 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-103256336-T-C is Benign according to our data. Variant chr11-103256336-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080463.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	NM_001080463.2	MANE Plus Clinical	c.10482+96T>C		intron	N/A	NP_001073932.1
	DYNC2H1	NM_001377.3	MANE Select	c.10461+96T>C		intron	N/A	NP_001368.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2H1	ENST00000650373.2	MANE Plus Clinical	c.10482+96T>C		intron	N/A	ENSP00000497174.1
	DYNC2H1	ENST00000375735.7	TSL:1 MANE Select	c.10461+96T>C		intron	N/A	ENSP00000364887.2
	DYNC2H1	ENST00000334267.11	TSL:1	c.2205+121917T>C		intron	N/A	ENSP00000334021.7

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9709 AN: 152072 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0447

GnomAD4 exome AF: 0.00609 AC: 6688 AN: 1098146 Hom.: 701 AF XY: 0.00534 AC XY: 2942 AN XY: 551116

African (AFR) AF: 0.231 AC: 5389 AN: 23328

American (AMR) AF: 0.0140 AC: 268 AN: 19122

Ashkenazi Jewish (ASJ) AF: 0.000193 AC: 4 AN: 20700

East Asian (EAS) AF: 0.00 AC: 0 AN: 33854

South Asian (SAS) AF: 0.000447 AC: 28 AN: 62676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42778

Middle Eastern (MID) AF: 0.0131 AC: 45 AN: 3436

European-Non Finnish (NFE) AF: 0.000256 AC: 216 AN: 845112

Other (OTH) AF: 0.0157 AC: 738 AN: 47140

GnomAD4 genome AF: 0.0639 AC: 9729 AN: 152190 Hom.: 1058 Cov.: 32 AF XY: 0.0607 AC XY: 4517 AN XY: 74436

African (AFR) AF: 0.223 AC: 9248 AN: 41480

American (AMR) AF: 0.0220 AC: 336 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68010

Other (OTH) AF: 0.0442 AC: 93 AN: 2102

Alfa AF: 0.0726 Hom.: 132

Bravo AF: 0.0734

Asia WGS AF: 0.0150 AC: 54 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12294076; hg19: chr11-103127065;