chr1-115060547-G-A

Position:

• chr1-115060547-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_005725.6(TSPAN2):​c.271-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,606,420 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (23 hom.)
• Consequence: TSPAN2 NM_005725.6 intron
• Scores: Splicing: ADA: 0.0001473
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.44

Genes affected

TSPAN2 (HGNC:20659): (tetraspanin 2) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-115060547-G-A is Benign according to our data. Variant chr1-115060547-G-A is described in ClinVar as [Benign]. Clinvar id is 769241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN2	NM_005725.6	c.271-9C>T		intron_variant		ENST00000369516.7	NP_005716.2
TSPAN2	NM_001308315.2	c.271-1566C>T		intron_variant			NP_001295244.1
TSPAN2	NM_001308316.2	c.271-9C>T		intron_variant			NP_001295245.1
TSPAN2	XM_016999996.2	c.271-1566C>T		intron_variant			XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN2	ENST00000369516.7	c.271-9C>T		intron_variant		1	NM_005725.6	ENSP00000358529.2
TSPAN2	ENST00000433172.3	c.253-9C>T		intron_variant		1		ENSP00000415256.1
TSPAN2	ENST00000369515.6	c.271-1566C>T		intron_variant		3		ENSP00000358528.2

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 601 AN: 152138 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00447 AC: 1107 AN: 247654 Hom.: 7 AF XY: 0.00456 AC XY: 611 AN XY: 133928

Gnomad AFR exome AF: 0.000504

Gnomad AMR exome AF: 0.00720

Gnomad ASJ exome AF: 0.0176

Gnomad EAS exome AF: 0.0000549

Gnomad SAS exome AF: 0.00428

Gnomad FIN exome AF: 0.000972

Gnomad NFE exome AF: 0.00428

Gnomad OTH exome AF: 0.00829

GnomAD4 exome AF: 0.00386 AC: 5618 AN: 1454164 Hom.: 23 Cov.: 28 AF XY: 0.00397 AC XY: 2872 AN XY: 723630

Gnomad4 AFR exome AF: 0.000994

Gnomad4 AMR exome AF: 0.00740

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00466

Gnomad4 FIN exome AF: 0.000806

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00509

GnomAD4 genome AF: 0.00395 AC: 601 AN: 152256 Hom.: 6 Cov.: 32 AF XY: 0.00414 AC XY: 308 AN XY: 74452

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00519

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00448 Hom.: 3

Bravo AF: 0.00436

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs189737200; hg19: chr1-115603168;