rs2569232

Variant names:

• chr5-172358888-A-G
• rs2569232
• NM_001017995.3:c.563-11T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-172358888-A-G
• chr5-172358888-A-C

Variant summary

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

The NM_001017995.3(SH3PXD2B):​c.563-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,611,944 control chromosomes in the GnomAD database, including 399,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41835 hom., cov: 32)
  • Exomes 𝑓: 0.70 (358012 hom.)
• Consequence: SH3PXD2B NM_001017995.3 intron
• Scores: Splicing: ADA: 0.00008617
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.549
• Publications: 11 publications found

Genes affected

SH3PXD2B (HGNC:29242): (SH3 and PX domains 2B) This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SH3PXD2B Gene-Disease associations (from GenCC):

• Frank-Ter Haar syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia, Genomics England PanelApp, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-172358888-A-G is Benign according to our data. Variant chr5-172358888-A-G is described in ClinVar as Benign. ClinVar VariationId is 257058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017995.3. 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
	SH3PXD2B	NM_001017995.3	MANE Select	c.563-11T>C		intron	N/A	NP_001017995.1	A1X283
	SH3PXD2B	NM_001308175.2		c.563-11T>C		intron	N/A	NP_001295104.1	G3V144

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3PXD2B	ENST00000311601.6	TSL:1 MANE Select	c.563-11T>C		intron	N/A	ENSP00000309714.5	A1X283
	SH3PXD2B	ENST00000519643.5	TSL:1	c.563-11T>C		intron	N/A	ENSP00000430890.1	G3V144
	SH3PXD2B	ENST00000918640.1		c.563-11T>C		intron	N/A	ENSP00000588699.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112152 AN: 151988 Hom.: 41782 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.732 AC: 181850 AN: 248446 AF XY: 0.733

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.770

Gnomad FIN exome AF: 0.656

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.716

GnomAD4 exome AF: 0.698 AC: 1018910 AN: 1459836 Hom.: 358012 Cov.: 37 AF XY: 0.702 AC XY: 509572 AN XY: 726146

African (AFR) AF: 0.843 AC: 28175 AN: 33430

American (AMR) AF: 0.768 AC: 34206 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 19363 AN: 26084

East Asian (EAS) AF: 0.750 AC: 29709 AN: 39636

South Asian (SAS) AF: 0.859 AC: 73878 AN: 86036

European-Finnish (FIN) AF: 0.661 AC: 35205 AN: 53300

Middle Eastern (MID) AF: 0.739 AC: 4257 AN: 5762

European-Non Finnish (NFE) AF: 0.676 AC: 750594 AN: 1110756

Other (OTH) AF: 0.722 AC: 43523 AN: 60306

GnomAD4 genome AF: 0.738 AC: 112263 AN: 152108 Hom.: 41835 Cov.: 32 AF XY: 0.738 AC XY: 54902 AN XY: 74354

African (AFR) AF: 0.843 AC: 34989 AN: 41526

American (AMR) AF: 0.731 AC: 11174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2582 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3979 AN: 5154

South Asian (SAS) AF: 0.856 AC: 4124 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6932 AN: 10566

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46198 AN: 67976

Other (OTH) AF: 0.714 AC: 1510 AN: 2114

Alfa AF: 0.700 Hom.: 166291

Bravo AF: 0.743

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Frank-Ter Haar syndrome (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.026
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: rs2569232; hg19: chr5-171785892;