chr5-172339475-GCCGCTC-G

Variant names:

• chr5-172339475-GCCGCTC-G
• rs534091900
• NM_001017995.3:c.1624_1629delGAGCGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001017995.3(SH3PXD2B):​c.1624_1629delGAGCGG​(p.Glu542_Arg543del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000946 in 1,613,808 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: SH3PXD2B NM_001017995.3 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.74

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-172339475-GCCGCTC-G is Benign according to our data. Variant chr5-172339475-GCCGCTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 284621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-172339475-GCCGCTC-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00509 (776/152308) while in subpopulation AFR AF= 0.0176 (730/41566). AF 95% confidence interval is 0.0165. There are 5 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3PXD2B	NM_001017995.3	c.1624_1629delGAGCGG	p.Glu542_Arg543del	conservative_inframe_deletion	Exon 13 of 13	ENST00000311601.6	NP_001017995.1
SH3PXD2B	XM_017009351.2	c.1708_1713delGAGCGG	p.Glu570_Arg571del	conservative_inframe_deletion	Exon 14 of 14		XP_016864840.1
SH3PXD2B	NM_001308175.2	c.1188+6655_1188+6660delGAGCGG		intron_variant	Intron 12 of 12		NP_001295104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3PXD2B	ENST00000311601.6	c.1624_1629delGAGCGG	p.Glu542_Arg543del	conservative_inframe_deletion	Exon 13 of 13	1	NM_001017995.3	ENSP00000309714.5
SH3PXD2B	ENST00000519643.5	c.1188+6655_1188+6660delGAGCGG		intron_variant	Intron 12 of 12	1		ENSP00000430890.1
SH3PXD2B	ENST00000636523.1	c.1227+6655_1227+6660delGAGCGG		intron_variant	Intron 13 of 13	5		ENSP00000490082.1
SH3PXD2B	ENST00000518522.5	c.199-5712_199-5707delGAGCGG		intron_variant	Intron 3 of 3	5		ENSP00000428076.1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152190 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00130 AC: 327 AN: 250982 Hom.: 4 AF XY: 0.000921 AC XY: 125 AN XY: 135750

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000514 AC: 751 AN: 1461500 Hom.: 3 AF XY: 0.000411 AC XY: 299 AN XY: 727008

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000639

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152308 Hom.: 5 Cov.: 33 AF XY: 0.00474 AC XY: 353 AN XY: 74478

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00586

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 09, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 17, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs534091900; hg19: chr5-171766479;