chr11-85707441-G-A

Variant names:

• chr11-85707441-G-A
• rs112099986
• NM_206927.4:c.6006C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_206927.4(SYTL2):​c.6006C>T​(p.Asn2002Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000621 in 1,612,848 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (8 hom.)
• Consequence: SYTL2 NM_206927.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412
• Publications: 1 publications found

Genes affected

SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-85707441-G-A is Benign according to our data. Variant chr11-85707441-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206927.4. 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
	SYTL2	NM_206927.4	MANE Select	c.6006C>T	p.Asn2002Asn	synonymous	Exon 15 of 20	NP_996810.2	A0A8J9FM55
	SYTL2	NM_001394447.1		c.6003C>T	p.Asn2001Asn	synonymous	Exon 15 of 20	NP_001381376.1
	SYTL2	NM_001394448.1		c.5958C>T	p.Asn1986Asn	synonymous	Exon 14 of 19	NP_001381377.1	A0A0U1RR07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYTL2	ENST00000359152.10	TSL:1 MANE Select	c.6006C>T	p.Asn2002Asn	synonymous	Exon 15 of 20	ENSP00000352065.7	A0A8J9FM55
	SYTL2	ENST00000528231.5	TSL:1	c.2091C>T	p.Asn697Asn	synonymous	Exon 13 of 18	ENSP00000431701.1	Q9HCH5-1
	SYTL2	ENST00000389960.8	TSL:1	c.2019C>T	p.Asn673Asn	synonymous	Exon 14 of 19	ENSP00000374610.4	Q9HCH5-6

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000641 AC: 161 AN: 251174 AF XY: 0.000604

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.000986

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000551 AC: 805 AN: 1460628 Hom.: 8 Cov.: 30 AF XY: 0.000524 AC XY: 381 AN XY: 726676

African (AFR) AF: 0.00673 AC: 225 AN: 33440

American (AMR) AF: 0.00123 AC: 55 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39650

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86170

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53394

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5764

European-Non Finnish (NFE) AF: 0.000316 AC: 351 AN: 1111058

Other (OTH) AF: 0.00199 AC: 120 AN: 60356

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152220 Hom.: 1 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74450

African (AFR) AF: 0.00381 AC: 158 AN: 41520

American (AMR) AF: 0.000981 AC: 15 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68006

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.000716 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-0.41
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs112099986; hg19: chr11-85418484;