9-92718920-G-C

Variant names:

• chr9-92718920-G-C
• rs201343832
• NM_001003800.2:c.1725C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001003800.2(BICD2):​c.1725C>G​(p.Pro575Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,606,936 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P575P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.65
• Publications: 0 publications found

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]

BICD2 Gene-Disease associations (from GenCC):

• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-92718920-G-C is Benign according to our data. Variant chr9-92718920-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 439433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000657 (10/152288) while in subpopulation SAS AF = 0.00124 (6/4832). AF 95% confidence interval is 0.000541. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003800.2. 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
	BICD2	NM_001003800.2	MANE Select	c.1725C>G	p.Pro575Pro	synonymous	Exon 5 of 7	NP_001003800.1
	BICD2	NM_015250.4		c.1725C>G	p.Pro575Pro	synonymous	Exon 5 of 8	NP_056065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	ENST00000356884.11	TSL:1 MANE Select	c.1725C>G	p.Pro575Pro	synonymous	Exon 5 of 7	ENSP00000349351.6
	BICD2	ENST00000375512.3	TSL:1	c.1725C>G	p.Pro575Pro	synonymous	Exon 5 of 8	ENSP00000364662.3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000202 AC: 47 AN: 233224 AF XY: 0.000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000782

Gnomad OTH exome AF: 0.000520

GnomAD4 exome AF: 0.000134 AC: 195 AN: 1454648 Hom.: 1 Cov.: 32 AF XY: 0.000164 AC XY: 119 AN XY: 723446

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.0000450 AC: 2 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00127 AC: 109 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49880

Middle Eastern (MID) AF: 0.000804 AC: 4 AN: 4974

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1110336

Other (OTH) AF: 0.000150 AC: 9 AN: 60100

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000383 Hom.: 0

Bravo AF: 0.0000567

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.013
DANN	Benign	0.57
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201343832; hg19: chr9-95481202; COSMIC: COSV105914480;