chr17-28661818-C-T

Variant names:

• chr17-28661818-C-T
• rs767513636
• NM_006923.4:c.59G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006923.4(SDF2):​c.59G>A​(p.Ser20Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S20T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SDF2 NM_006923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 2 publications found

Genes affected

SDF2 (HGNC:10675): (stromal cell derived factor 2) The protein encoded by this gene is believed to be a secretory protein. It has regions of similarity to hydrophilic segments of yeast mannosyltransferases. Its expression is ubiquitous and the gene appears to be relatively conserved among mammals. Alternate splicing results in both coding and non-coding variants. A pseudogene of this gene is located on chromosome 15. [provided by RefSeq, Dec 2011]

SUPT6H (HGNC:11470): (SPT6 homolog, histone chaperone and transcription elongation factor) Enables histone binding activity. Involved in negative regulation of histone H3-K27 methylation and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be located in nucleoplasm. Predicted to be part of transcription elongation factor complex. Predicted to be active in transcriptionally active chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026697487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006923.4. 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
	SDF2	NM_006923.4	MANE Select	c.59G>A	p.Ser20Asn	missense	Exon 1 of 3	NP_008854.2
	SDF2	NR_045585.2		n.149+228G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF2	ENST00000247020.9	TSL:1 MANE Select	c.59G>A	p.Ser20Asn	missense	Exon 1 of 3	ENSP00000247020.3	Q99470
	SDF2	ENST00000585428.1	TSL:1	n.99G>A		non_coding_transcript_exon	Exon 1 of 2
	SDF2	ENST00000893452.1		c.59G>A	p.Ser20Asn	missense	Exon 1 of 4	ENSP00000563511.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251424 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.31
DANN	Benign	0.91
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.11
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.21
Sift	Benign	0.67	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.41		Loss of glycosylation at S20 (P = 0.0372)
MVP		0.13
MPC		0.40
ClinPred		0.029	T
GERP RS		-2.7
PromoterAI		-0.034	Neutral
Varity_R		0.062
gMVP		0.20

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: rs767513636; hg19: chr17-26988836;