rs41271220

Variant names:

• chr7-158918748-C-T
• rs41271220
• NM_018051.5:c.1800C>T
• DYNC2I1 p.Ala600Ala

Your query was ambiguous. Multiple possible variants found:

• chr7-158918748-C-T
• chr7-158918748-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018051.5(DYNC2I1):​c.1800C>T​(p.Ala600Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,613,468 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 33)
  • Exomes 𝑓: 0.019 (326 hom.)
• Consequence: DYNC2I1 NM_018051.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.584
• Publications: 2 publications found

Genes affected

DYNC2I1 (HGNC:21862): (dynein 2 intermediate chain 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

DYNC2I1 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 8 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Jeune syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-158918748-C-T is Benign according to our data. Variant chr7-158918748-C-T is described in ClinVar as Benign. ClinVar VariationId is 474623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.584 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0123 (1875/152132) while in subpopulation NFE AF = 0.0213 (1448/68006). AF 95% confidence interval is 0.0204. There are 22 homozygotes in GnomAd4. There are 846 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018051.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	NM_018051.5	MANE Select	c.1800C>T	p.Ala600Ala	synonymous	Exon 15 of 25	NP_060521.4
	DYNC2I1	NM_001350914.2		c.1662C>T	p.Ala554Ala	synonymous	Exon 15 of 25	NP_001337843.1
	DYNC2I1	NM_001350915.2		c.1227C>T	p.Ala409Ala	synonymous	Exon 14 of 24	NP_001337844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC2I1	ENST00000407559.8	TSL:1 MANE Select	c.1800C>T	p.Ala600Ala	synonymous	Exon 15 of 25	ENSP00000384290.3	Q8WVS4
	DYNC2I1	ENST00000444851.5	TSL:1	n.1131C>T		non_coding_transcript_exon	Exon 11 of 20	ENSP00000392608.1	H7C022
	DYNC2I1	ENST00000860814.1		c.1875C>T	p.Ala625Ala	synonymous	Exon 16 of 26	ENSP00000530873.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1875 AN: 152014 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00482

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.00528

GnomAD2 exomes AF: 0.0127 AC: 3163 AN: 249138 AF XY: 0.0131

Gnomad AFR exome AF: 0.00317

Gnomad AMR exome AF: 0.00672

Gnomad ASJ exome AF: 0.00845

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00594

Gnomad NFE exome AF: 0.0212

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.0189 AC: 27578 AN: 1461336 Hom.: 326 Cov.: 31 AF XY: 0.0185 AC XY: 13477 AN XY: 726916

African (AFR) AF: 0.00281 AC: 94 AN: 33478

American (AMR) AF: 0.00700 AC: 313 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 211 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00631 AC: 544 AN: 86244

European-Finnish (FIN) AF: 0.00734 AC: 391 AN: 53288

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.0225 AC: 25061 AN: 1111652

Other (OTH) AF: 0.0156 AC: 939 AN: 60358

GnomAD4 genome AF: 0.0123 AC: 1875 AN: 152132 Hom.: 22 Cov.: 33 AF XY: 0.0114 AC XY: 846 AN XY: 74372

African (AFR) AF: 0.00359 AC: 149 AN: 41496

American (AMR) AF: 0.00681 AC: 104 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3464

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4822

European-Finnish (FIN) AF: 0.00482 AC: 51 AN: 10572

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1448 AN: 68006

Other (OTH) AF: 0.00522 AC: 11 AN: 2106

Alfa AF: 0.0180 Hom.: 48

Bravo AF: 0.0122

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Short-rib thoracic dysplasia 8 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.17
DANN	Benign	0.24
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41271220;

hg19: chr7-158711439;