9-92715325-G-A

Position:

• chr9-92715325-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001003800.2(BICD2):​c.2397C>T​(p.Leu799Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000639 in 1,612,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.911

Genes affected

BICD2 (HGNC:17208): (BICD cargo adaptor 2) This gene is one of two human homologs of Drosophila bicaudal-D and a member of the Bicoid family. It has been implicated in dynein-mediated, minus end-directed motility along microtubules. It has also been reported to be a phosphorylation target of NIMA related kinase 8. Two alternative splice variants have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-92715325-G-A is Benign according to our data. Variant chr9-92715325-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92715325-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.911 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000591 (90/152374) while in subpopulation NFE AF= 0.000926 (63/68034). AF 95% confidence interval is 0.000742. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.2397C>T	p.Leu799Leu	synonymous_variant	7/7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.2397C>T	p.Leu799Leu	synonymous_variant	7/8		NP_056065.1
BICD2	XM_017014551.2	c.2478C>T	p.Leu826Leu	synonymous_variant	7/8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.2397C>T	p.Leu799Leu	synonymous_variant	7/7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.2397C>T	p.Leu799Leu	synonymous_variant	7/8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000631 AC: 157 AN: 248692 Hom.: 0 AF XY: 0.000607 AC XY: 82 AN XY: 135102

Gnomad AFR exome AF: 0.0000630

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00224

Gnomad NFE exome AF: 0.000849

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000644 AC: 940 AN: 1460576 Hom.: 1 Cov.: 32 AF XY: 0.000663 AC XY: 482 AN XY: 726632

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00273

Gnomad4 NFE exome AF: 0.000675

Gnomad4 OTH exome AF: 0.000597

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152374 Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40 AN XY: 74508

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.000363

EpiCase AF: 0.000872

EpiControl AF: 0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	BICD2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2020	- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.4
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs151133287; hg19: chr9-95477607; COSMIC: COSV104670514;