20-19886612-C-CTT

Position:

• chr20-19886612-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018993.4(RIN2):​c.-36-2936_-36-2935dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., cov: 0)
  • Exomes 𝑓: 0.0061 (0 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844

Genes affected

RIN2 (HGNC:18750): (Ras and Rab interactor 2) The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-19886612-C-CTT is Benign according to our data. Variant chr20-19886612-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 1185800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1236/115156) while in subpopulation AFR AF= 0.0216 (636/29406). AF 95% confidence interval is 0.0202. There are 19 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4	c.-36-2936_-36-2935dup		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-2936_-36-2935dup		intron_variant		2	NM_018993.4	P1
RIN2	ENST00000648440.1	c.-187_-186dup		5_prime_UTR_variant	1/12			P1
RIN2	ENST00000432334.2	n.537-2936_537-2935dup		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.618-2936_618-2935dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1236 AN: 115168 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00450

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00467

Gnomad SAS AF: 0.00733

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00829

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00610 AC: 2468 AN: 404514 Hom.: 0 Cov.: 0 AF XY: 0.00619 AC XY: 1353 AN XY: 218592

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.00811

Gnomad4 ASJ exome AF: 0.00371

Gnomad4 EAS exome AF: 0.00762

Gnomad4 SAS exome AF: 0.00832

Gnomad4 FIN exome AF: 0.00375

Gnomad4 NFE exome AF: 0.00572

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.0107 AC: 1236 AN: 115156 Hom.: 19 Cov.: 0 AF XY: 0.0102 AC XY: 552 AN XY: 54154

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00450

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00469

Gnomad4 SAS AF: 0.00738

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00829

Gnomad4 OTH AF: 0.0143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11362637; hg19: chr20-19867256;