22-24419434-TAAGGGCCAAGCAGAAAAG-T

Position:

• chr22-24419434-TAAGGGCCAAGCAGAAAAG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000358654.2(SPECC1L-ADORA2A):​n.*861+4701_*861+4718delCAGAAAAGAAGGGCCAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 151,974 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0065 (3 hom., cov: 31)
• Consequence: SPECC1L-ADORA2A ENST00000358654.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

Genes affected

SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]

ADORA2A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 22-24419434-TAAGGGCCAAGCAGAAAAG-T is Benign according to our data. Variant chr22-24419434-TAAGGGCCAAGCAGAAAAG-T is described in ClinVar as [Benign]. Clinvar id is 1695039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPECC1L-ADORA2A	NR_103546.1	n.3905+4701_3905+4718delCAGAAAAGAAGGGCCAAG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPECC1L-ADORA2A	ENST00000358654.2	n.*861+4701_*861+4718delCAGAAAAGAAGGGCCAAG		intron_variant		2		ENSP00000351480.2
ADORA2A	ENST00000467385.5	n.381+1186_381+1203delCAGAAAAGAAGGGCCAAG		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 994 AN: 151856 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0146

Gnomad FIN AF: 0.00265

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00720

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00654 AC: 994 AN: 151974 Hom.: 3 Cov.: 31 AF XY: 0.00602 AC XY: 447 AN XY: 74296

Gnomad4 AFR AF: 0.00179

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.00265

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00686 Hom.: 1

Bravo AF: 0.00653

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

SPECC1L: BS1, BS2 -

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: rs548830344; hg19: chr22-24815402;