rs138300993

chr9-92718839-C-T

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.1806G>A(p.Thr602=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,609,478 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.747

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=-0.88).
• BP6: Variant 9-92718839-C-T is Benign according to our data. Variant chr9-92718839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92718839-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.747 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00113 (172/152306) while in subpopulation NFE AF= 0.00151 (103/68004). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD2	NM_001003800.2	c.1806G>A	p.Thr602=	synonymous_variant	5/7	ENST00000356884.11
BICD2	NM_015250.4	c.1806G>A	p.Thr602=	synonymous_variant	5/8
BICD2	XM_017014551.2	c.1887G>A	p.Thr629=	synonymous_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD2	ENST00000356884.11	c.1806G>A	p.Thr602=	synonymous_variant	5/7	1	NM_001003800.2	A2
BICD2	ENST00000375512.3	c.1806G>A	p.Thr602=	synonymous_variant	5/8	1		P4

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00128 AC: 301 AN: 234442 Hom.: 1 AF XY: 0.00117 AC XY: 150 AN XY: 128132

Gnomad AFR exome AF: 0.000337

Gnomad AMR exome AF: 0.000301

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000662

Gnomad FIN exome AF: 0.000148

Gnomad NFE exome AF: 0.00148

Gnomad OTH exome AF: 0.000863

GnomAD4 exome AF: 0.00118 AC: 1715 AN: 1457172 Hom.: 4 Cov.: 32 AF XY: 0.00113 AC XY: 816 AN XY: 724756

Gnomad4 AFR exome AF: 0.000360

Gnomad4 AMR exome AF: 0.000524

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000697

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00158

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74474

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00220 Hom.: 1

Bravo AF: 0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 04, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	BICD2: BP4, BP7 -

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

Invitae

Jan 31, 2024

- -

BICD2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 02, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.30
Dann	Benign	0.44

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: rs138300993; hg19: chr9-95481121;